Method for synthesizing benzo [d] imidazole [2, 1-b] thiazole

Abstract

The invention discloses a method for synthesizing benzo [d] imidazole [2, 1-b] thiazole, which specifically comprises the following steps of: reacting 2H-aza-allylene, o-bromo aryl isothiocyanate, an organic solvent and alkali in a stirring state, extracting and separating liquid after the reaction is finished, washing, drying, concentrating, and carrying out column chromatography separation to obtain the benzo [d] imidazole [2, 1-b] thiazole. Compared with the prior art, the method for synthesizing the benzo [d] imidazole [2, 1-b] thiazole has the advantages that sulfur-containing aza-fused aromatic hydrocarbon which is commonly used at present is not needed as a substrate, a metal catalyst is not needed, illumination is not needed, and an expensive photocatalyst is not needed; the cost is low and the process is green; the synthesis route is novel in design, the operation method is simple, more target products with abundant structures can be directly obtained through reaction under mild conditions, the method has important guiding significance in theory and practice for expanding the synthesis route of the benzo [d] imidazole [2, 1-b] thiazole compound, and the application prospect is good.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and relates to a method for synthesizing benzo[d]imidazo[2,1-b]thiazole. In particular, it relates to a new method for obtaining benzo[d]imidazo[2,1-b]thiazole under metal-free conditions in a mild and efficient manner, using o-bromoaryl isothiocyanate as a sulfur source and o-bromoaryl isothiocyanate and 2H-aziridine as substrates. Background Art

[0002] The benzo[d]imidazo[2,1-b]thiazole skeleton plays an important role in medicinal chemistry and materials science. Research shows that derivatives containing the benzo[d]imidazo[2,1-b]thiazole skeleton can inhibit cancer cell proliferation and induce their apoptosis, showing potential anti-cancer effects. In addition, such derivatives also exhibit significant activities against drug-resistant strains and viruses. Therefore, it can be predicted that compounds containing this type of structure will also have very broad application prospects in the future in the fields of new drug development, materials innovation, and green chemistry.

[0003] In recent years, the remarkable biological and pharmaceutical properties of compounds containing the benzimidazo[2,1-b]thiazole structure have stimulated the synthetic interest of organic chemists. Fortunately, significant progress has also been made in methods for constructing such high-value sulfur-nitrogen heterocyclic systems. Specifically, the traditional method for constructing the benzimidazo[2,1-b]thiazole skeleton is to use 2-mercaptoimidazole and o-dihaloarenes as substrates to obtain it through a catalytic coupling reaction (Org. Biomol. Chem. 2012, 10, 7944–7948.). However, the narrow scope of the substrate 2-mercaptoimidazole in this type of method limits the further widespread application of this method. Recently, a series of synthetic strategies for constructing such skeletons have also been successfully developed using 2-aminobenzothiazole as a substrate. For example, the Volkova group and the Chai group respectively demonstrated the synthesis of benzimidazo[2,1-b]thiazole from 2-aminobenzothiazole, benzaldehyde, and alkyne using a Cu catalyst (J. Org. Chem. 2017, 82, 9682−9692.; Tetrahedron 2019, 75, 1052-1063.). The Hajra group found that under air oxidation, Fe / Zn salts can catalyze the cyclization reaction of 2-aminobenzothiazole and ketones to form the target product (Org. Lett. 2014, 16, 6084−6087.). The Shankar group found that the regioselective reaction of 2-aminobenzothiazole and alkyne under β-CD / Cu catalysis gives iodo-substituted benzimidazo[2,1-b]benzothiazole (Tetrahedron 2017, 73, 4295−4306.). Deng and his colleagues reported a metal-free oxidative cyclization reaction for the one-pot synthesis of benzimidazo[2,1-b]thiazole from 2-aminobenzothiazole and cyclic ketones promoted by oxygen and elemental sulfur (Green Chem. 2017, 19, 4294–4298.). Meanwhile, MesHram used a mild and novel method to synthesize functionalized benzimidazole analogues in an ionic liquid from 2-aminobenzothiazole and β-nitroacrylate under solvent-free and catalyst-free conditions (Tetrahedron Lett. 2014, 55, 3473–3477.). In addition, the Zhu group reported the cyclization addition of Cu(OAc)2-catalyzed α-methylenyl isocyanide with benzothiazole, followed by rearrangement to obtain benzimidazo[2,1-b]thiazole (Org. Lett. 2015, 17, 5336−5339.).In 2024, the Biswas group discovered a new synthetic method using TfOH-catalyzed 2H-aziridine and 2-mercaptopyridine as substrates, in which regioselective ring-opening reaction occurred to synthesize benzo[d]imidazo[2,1-b]thiazole (Org. Biomol. Chem. 2024, 22, 4697–4703.). Despite the great achievements in the strategies for synthesizing target heterocycles, the above-reported method still has many disadvantages, such as narrow substrate scope, relatively single source of raw materials (sulfur-containing benzoazarenes are essential), and the necessity to use pre-functionalized and commercially unavailable reactants as substrates.

[0004] Therefore, it is of great practical significance to develop a method with simple operation for synthesizing functionalized benzo[d]imidazo[2,1-b]thiazole using readily available and structurally diverse substrates. Summary of the Invention

[0005] Due to the above defects in the prior art, the present invention provides a method for synthesizing benzo[d]imidazo[2,1-b]thiazole with simple operation and readily available reactants, which overcomes the defects of long reaction time, low yield, severe reaction conditions, use of toxic and expensive metal catalysts / ligands, and difficulty in removing trace transition metals from the reaction mixture existing in the current preparation methods of benzo[d]imidazo[2,1-b]thiazole.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] A method for synthesizing benzo[d]imidazo[2,1-b]thiazole, in which 2H-aziridine, o-bromoaryl isothiocyanate, organic solvent and base react under stirring, and after the reaction is completed, extraction, liquid separation, washing, drying, concentration and column chromatography separation are carried out to obtain benzo[d]imidazo[2,1-b]thiazole.

[0008] The reaction equation of the present invention is shown as follows:

[0009]

[0010] The substituents in the above formula: R 1 and R 2 are mainly hydrogen, methyl, ethyl, methoxy, fluorine, chlorine and thiophenyl; R 3 is mainly electron-withdrawing groups and electron-donating groups such as hydrogen, nitro, methoxy, fluorine, chlorine, bromine, etc.

[0011] The present invention adopts a one-step reaction method of 2H-aziridine compound and isothiocyanate compound to obtain benzo[d]imidazo[2,1-b]thiazole compounds with different substituents. Its reactants are readily available, the synthesis conditions are relatively simple and the steps are simple, and it has good application prospects.

[0012] As a preferred technical solution:

[0013] For a method for synthesizing benzo[d]imidazo[2,1-b]thiazole as described above, the temperature of the reaction is 100 °C and the duration is 16 h;

[0014] After the reaction is completed, water is added for quenching, and dichloromethane is added for dilution, followed by stirring;

[0015] The aqueous phase obtained by extraction and liquid separation is washed with dichloromethane 2 - 3 times, and the organic phase obtained by extraction and liquid separation is washed with saturated brine.

[0016] For a method for synthesizing benzo[d]imidazo[2,1-b]thiazole as described above, the 2H-azirine is at least one of 2,3-diphenyl-2H-azirine, 2-phenyl-3-p-tolyl-2H-azirine, 3-(4-ethylphenyl)-2-phenyl-2H-azirine, 3-(4-methoxyphenyl)-2-phenyl-2H-azirine, 3-(4-fluorophenyl)-2-phenyl-2H-azirine, 3-(4-chlorophenyl)-2-phenyl-2H-azirine, 3-(4-bromophenyl)-2-phenyl-2H-azirine, 2-phenyl-3-(5,6,7,8-tetrahydronaphthalen-2-yl)-2H-azirine, 3-phenyl-2-p-tolyl-2H-azirine, and 2-(4-chlorophenyl)-3-phenyl-2H-azirine.

[0017] For a method for synthesizing benzo[d]imidazo[2,1-b]thiazole as described above, the o-bromoaryl isothiocyanate is at least one of 1-bromo-2-isothiocyanatobenzene, 2-bromo-4-fluoro-1-isothiocyanatobenzene, 2,4-dibromo-1-isothiocyanatobenzene, 2-bromo-1-isothiocyanato-4-methylbenzene, 2-bromo-4-chloro-1-isothiocyanatobenzene, 1-bromo-4-chloro-2-isothiocyanatobenzene, 1-bromo-2-isothiocyanato-4-methylbenzene, 2-bromo-1-isothiocyanato-4-methoxybenzene, 1-chloro-2-isothiocyanatobenzene, and 2-bromo-1-isothiocyanato-4-nitrobenzene.

[0018] For a method for synthesizing benzo[d]imidazo[2,1-b]thiazole as described above, the organic solvent is at least one of N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dichloromethane, tetrahydrofuran, and acetonitrile.

[0019] A method for synthesizing benzimidazo[2,1-b]thiazole as described above, wherein the base is at least one of cesium carbonate, triethylamine, sodium hydride, sodium bicarbonate, potassium hydroxide, 1,4-diazabicyclo[2.2.2]octane, and 1,8-diazabicycloundec-7-ene.

[0020] A method for synthesizing benzimidazo[2,1-b]thiazole as described above, wherein the molar ratio of 2H-aziridine, o-bromoaryl isothiocyanate, and the base is 1:1:1.

[0021] A method for synthesizing benzimidazo[2,1-b]thiazole as described above, wherein the organic phase obtained by extraction and liquid separation is dried with anhydrous sodium sulfate after washing.

[0022] A method for synthesizing benzimidazo[2,1-b]thiazole as described above, wherein the eluent used for column chromatography separation is a mixture of petroleum ether and ethyl acetate.

[0023] A method for synthesizing benzimidazo[2,1-b]thiazole as described above, wherein the volume ratio of petroleum ether to ethyl acetate in the eluent is 10:1 to 30:1.

[0024] The above technical solutions are only one feasible technical solution of the present invention, and the protection scope of the present invention is not limited thereto. Those skilled in the art can reasonably adjust the specific design according to actual needs.

[0025] The above invention has the following advantages or beneficial effects:

[0026] (1) The method for synthesizing benzimidazo[2,1-b]thiazole of the present invention has a mild and efficient synthesis strategy;

[0027] (2) The method for synthesizing benzimidazo[2,1-b]thiazole of the present invention does not require the use of sulfur and nitrogen heterocyclic fused aromatics reported in the prior art as substrates, does not require metal catalysts, does not require light, does not require expensive photocatalysts, and has mild reaction conditions;

[0028] (3) The method for synthesizing benzimidazo[2,1-b]thiazole of the present invention adopts a "one-pot method" with low cost and low toxicity, eliminates the need for toxic reagents, provides a greener and more sustainable alternative, greatly improves the reaction efficiency, has simple post-treatment, and has good industrial application prospects. Brief Description of the Drawings

[0029] The present invention, its features, shapes and advantages will become more apparent by reading the following detailed description of non-limiting embodiments with reference to the accompanying drawings. The same reference numerals in all the drawings indicate the same parts. The drawings are not necessarily drawn to scale, and the emphasis is on showing the gist of the present invention.

[0030] Figure 1 Single crystal spectrum of the product (7-methoxy-2,3-diphenyl)benzo[d]imidazo[2,1-b]thiazole prepared in Example 14;

[0031] Figure 2 1H nuclear magnetic resonance spectrum of the product (7-methoxy-2,3-diphenyl)benzo[d]imidazo[2,1-b]thiazole prepared in Example 14;

[0032] Figure 3 13C nuclear magnetic resonance spectrum of the product (7-methoxy-2,3-diphenyl)benzo[d]imidazo[2,1-b]thiazole prepared in Example 14. Detailed implementation manners

[0033] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, but it is not intended to limit the present invention.

[0034] In the following examples, the chemical equation for the synthesis of benzo[d]imidazo[2,1-b]thiazole from 2H-aziridine and o-bromoaryl isothiocyanate is as follows:

[0035]

[0036] Specifically:

[0037] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-diphenyl-2H-aziridine, 0.5 mmol of o-bromoaryl isothiocyanate, and 0.5 mmol of cesium carbonate into a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with saturated brine, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the liquid. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine. Dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and then perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1 - 60:1) as the eluent to obtain the final product, benzo[d]imidazo[2,1-b]thiazole compounds with different substituents.

[0038] Example 1

[0039] The preparation method of 2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0040] In a 10 ml dry round-bottom flask, 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-diphenyl-2H-azirine, 0.5 mmol of o-bromoaryl isothiocyanate, and 0.5 mmol of cesium carbonate were added. The reaction mixture was heated and stirred at 100 °C for 16 hours. After the reaction was completed, the reaction was quenched with water, diluted with dichloromethane, and stirred for 30 minutes. Then, liquid separation by extraction was carried out. The aqueous phase was washed with dichloromethane 2 - 3 times, and the organic phase was washed with saturated brine. The obtained organic phase was dried over anhydrous sodium sulfate, then filtered, concentrated under reduced pressure, and further separated by column chromatography using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 82%.

[0041] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.56(dd, J = 8.0, 1.2 Hz, 1H), 7.51 – 7.44 (m, 7H), 7.18 – 7.01 (m, 5H), 6.74 (d,J = 8.2 Hz, 1H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 147.14, 143.21, 134.11,133.05, 131.33, 130.52, 130.30, 129.54, 129.39, 128.30, 127.02, 126.98,125.78, 124.51, 124.26, 113.42. HRMS (ESI-FT) m / z: [M+Na] + Calcd forC 21 H 14 N2SNa 349.0769; Found 349.0767.

[0042] Example 2

[0043] The preparation method of 3-(4-ethylphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0044] In a 10 ml dry round-bottom flask, 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-ethylphenyl)-2-phenyl-2H-azirine, 0.5 mmol of o-bromoaryl isothiocyanate, and 0.5 mmol of cesium carbonate were added. The reaction mixture was heated and stirred at 100 °C for 16 hours. After the reaction was completed, the reaction was quenched with water, diluted with dichloromethane, and stirred for 30 minutes. The mixture was extracted and separated. The aqueous phase was washed with dichloromethane 2-3 times, and the organic phase was washed with saturated brine. The obtained organic phase was dried over anhydrous sodium sulfate, then filtered, concentrated under reduced pressure, and further separated by column chromatography using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 3-(4-ethylphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 76%.

[0045] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.0 Hz, 1H), 7.63 (dd, J = 6.8, 1.5 Hz, 2H), 7.53 – 7.46 (m, 2H), 7.42 (d, J = 7.4 Hz, 2H), 7.33 – 7.13 (m, 5H), 6.90 (d, J = 8.2 Hz, 1H), 2.85 (q, J = 7.6 Hz, 2H), 1.41 (td, J = 7.6, 1.6 Hz, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 146.95, 145.72, 143.05, 134.19, 133.12, 131.39, 131.17, 130.52, 129.33, 128.83, 128.25, 127.79, 127.32, 126.93, 125.74, 124.43, 124.20, 28.80, 15.28. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 23 H 18 N2SH 355.1263; Found 355.1266.

[0046] Example 3

[0047] The preparation method of 3-(4-methoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0048] In a 10 ml dry round-bottom flask, add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-methoxyphenyl)-2-phenyl-2H-azirine, 0.5 mmol of o-bromoaryl isothiocyanate, and 0.5 mmol of cesium carbonate. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 10:1) as the eluent to obtain the final product 3-(4-methoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 80%.

[0049] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.59(dd, J = 7.9, 1.3 Hz, 1H), 7.55 – 7.50 (m, 2H), 7.42 – 7.36 (m, 2H), 7.20 –7.14 (m, 3H), 7.14 – 7.05 (m, 2H), 7.03 – 6.99 (m, 2H), 6.79 (dd, J = 8.2,1.2 Hz, 1H), 3.86 (s, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 159.40, 145.81,142.00, 133.15, 132.06, 131.54, 129.47, 127.22, 125.87, 125.77, 124.71,123.39, 123.17, 123.08, 121.12, 113.76, 112.37, 54.36. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 22 H 16 N2OSH 357.1056; Found 357.1058.

[0050] Example 4

[0051] The preparation method of 3-(2,5-dimethoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0052] In a 10 ml dry round-bottom flask, add 2 ml of dimethyl sulfoxide, 2,3-bis(4-methoxyphenyl)-2H-azirine, 0.5 mmol of o-bromoaryl isothiocyanate, and 0.5 mmol of cesium carbonate. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 10:1) as the eluent to obtain the final product 3-(2,5-dimethoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 70%.

[0053] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.54(td, J = 8.6, 1.3 Hz, 3H), 7.20 – 7.04 (m, 4H), 7.03 – 6.93 (m, 2H), 6.85 (d,J = 3.0 Hz, 1H), 6.77 (dd, J = 8.1, 1.3 Hz, 1H), 3.63 (s, 3H), 3.54 (s, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 152.82, 151.71, 146.25, 142.42, 133.23,132.24, 129.32, 127.20, 125.85, 125.71, 124.74, 123.29, 122.94, 119.51,118.63, 117.01, 115.48, 112.19, 111.62, 55.05, 54.78. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 23 H 18 N2O2SH 387.1161; Found 387.1167.

[0054] Example 5

[0055] The preparation method of 3-phenyl-2-(p-tolyl)benzo[d]imidazo[2,1-b]thiazole is as follows:

[0056] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 2-phenyl-3-(p-tolyl)-2H-azirine, 0.5 mmol of o-bromoaryl isothiocyanate, and 0.5 mmol of cesium carbonate to a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 3-phenyl-2-(p-tolyl)benzo[d]imidazo[2,1-b]thiazole with a yield of 79%.

[0057] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.59(dd, J = 8.1, 1.2 Hz, 1H), 7.48 (s, 5H), 7.40 – 7.36 (m, 2H), 7.19 – 7.14 (m,1H), 7.06 (td, J = 7.9, 7.4, 1.3 Hz, 1H), 6.98 (d, J = 7.9 Hz, 2H), 6.76 (dd,J = 8.2, 1.2 Hz, 1H), 2.22 (s, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 146.99,143.21, 136.79, 133.07, 131.36, 131.12, 130.50, 130.37, 129.46, 129.33,129.02, 126.88, 125.75, 124.44, 124.24, 113.40, 21.20. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 22 H 16 N2SH 341.1106; Found 341.1113.

[0058] Example 6

[0059] A preparation method of 3-phenyl-2-(2-thienyl)benzo[d]imidazo[2,1-b]thiazole is as follows:

[0060] In a 10 ml dry round-bottom flask, add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-phenyl-2-(2-thienyl)-2H-azirine, 0.5 mmol of o-bromoaryl isothiocyanate, and 0.5 mmol of cesium carbonate. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 10:1) as the eluent to obtain the final product 3-phenyl-2-(2-thienyl)benzo[d]imidazo[2,1-b]thiazole with a yield of 68%.

[0061] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.64 –7.58 (m, 4H), 7.25 (dd, J = 3.5, 1.3 Hz, 1H), 7.24 – 7.19 (m, 4H), 7.19 –7.14 (m, 1H), 7.14 – 7.10 (m, 1H), 6.79 (dd, J = 8.1, 1.2 Hz, 1H). 13 C { 1 H}NMR (100 MHz, CDCl3) δ 147.02, 144.71, 132.60, 131.85, 131.54, 130.35,129.37, 129.12, 128.63, 127.31, 127.05, 126.39, 125.83, 125.00, 123.66,123.19. HRMS (ESI-FT) m / z: [M+Na] + Calcd for C 19 H 12 N2S2Na 355.0334; Found355.0340.

[0062] Example 7

[0063] The preparation method of 2,3-bis(p-tolyl)benzo[d]imidazo[2,1-b]thiazole is as follows:

[0064] In a 10 ml dry round-bottom flask, 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-bis(p-tolyl)-2H-azirine, 0.5 mmol of o-bromoaryl isothiocyanate, and 0.5 mmol of cesium carbonate were added. The reaction mixture was heated and stirred at 100 °C for 16 hours. After the reaction was completed, the reaction was quenched with water, diluted with dichloromethane, and stirred for 30 minutes. The layers were separated by extraction. The aqueous phase was washed with dichloromethane 2-3 times, and the organic phase was washed with saturated brine. The obtained organic phase was dried over anhydrous sodium sulfate, then filtered, concentrated under reduced pressure, and further separated by column chromatography using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 2,3-bis(p-tolyl)benzo[d]imidazo[2,1-b]thiazole with a yield of 75%.

[0065] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.58(dd, J = 8.0, 1.2 Hz, 1H), 7.42 – 7.37 (m, 2H), 7.35 (d, J = 8.0 Hz, 2H),7.27 (d, J = 7.9 Hz, 2H), 7.18 – 7.12 (m, 1H), 7.06 (td, J = 7.9, 7.4, 1.3Hz, 1H), 6.98 (d, J = 8.0 Hz, 2H), 6.79 (dd, J = 8.2, 1.2 Hz, 1H), 2.43 (s,3H), 2.22 (s, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 146.82, 143.11, 139.42,136.66, 133.15, 131.16, 130.49, 130.07, 128.99, 127.25, 126.81, 125.70,124.36, 124.18, 124.00, 113.45, 21.59, 21.20. HRMS (ESI-FT) m / z: [M+H] + Calcdfor C 23 H 18 N2SH 355.1263; Found 355.1266.

[0066] Example 8

[0067] The preparation method of 3-(4-chlorophenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0068] In a 10 ml dry round-bottom flask, add 2 ml of dimethyl sulfoxide, 0.5 mmol of 2-(4-chlorophenyl)-3-phenyl-2H-azirine, 0.5 mmol of o-bromoaryl isothiocyanate, and 0.5 mmol of cesium carbonate. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 3-(4-chlorophenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 74%.

[0069] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.62(dd, J = 7.9, 1.2 Hz, 1H), 7.52 – 7.40 (m, 7H), 7.23 – 7.10 (m, 4H), 6.82(dd, J = 8.2, 1.1 Hz, 1H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 147.51, 143.52,135.70, 133.63, 132.88, 132.67, 130.54, 129.75, 128.69, 128.40, 127.31,127.07, 125.91, 124.73, 124.41, 122.92, 113.32. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 21 H 13 N2SClH 361.0560; Found 361.0565.

[0070] Example 9

[0071] The preparation method of 3-(4-fluorophenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0072] In a 10 ml dry round-bottom flask, add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-fluorophenyl)-2-phenyl-2H-azirine, 0.5 mmol of o-bromoaryl isothiocyanate, and 0.5 mmol of cesium carbonate. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 3-(4-fluorophenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 62%.

[0073] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.63(dd, J = 8.1, 1.2 Hz, 1H), 7.51 – 7.45 (m, 4H), 7.24 – 7.18 (m, 5H), 7.18 –7.10 (m, 2H), 6.77 (dd, J = 8.3, 1.2 Hz, 1H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ164.73, 133.34, 133.25, 132.86, 132.59, 130.55, 129.97, 128.41, 127.33,125.94, 124.78, 124.42, 116.81, 116.59, 113.31. 19 F NMR (376 MHz, CDCl3) δ -100.18, -105.56, -110.65. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 21 H 13 N2SFH345.0856; Found 345.0863.

[0074] Example 10

[0075] The preparation method of 2-(4-chlorophenyl)-3-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0076] In a 10 ml dry round-bottom flask, 2 ml of dimethyl sulfoxide, 0.5 mmol of 2-(4-chlorophenyl)-3-phenyl-2H-azirine, 0.5 mmol of o-bromoaryl isothiocyanate, and 0.5 mmol of cesium carbonate were added. The reaction mixture was heated and stirred at 100 °C for 16 hours. After the reaction was completed, the reaction was quenched with water, diluted with dichloromethane, and stirred for 30 minutes. The layers were separated by extraction. The aqueous phase was washed with dichloromethane 2-3 times, and the organic phase was washed with saturated brine. The obtained organic phase was dried over anhydrous sodium sulfate, then filtered, concentrated under reduced pressure, and further separated by column chromatography using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 2-(4-chlorophenyl)-3-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 80%.

[0077] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.59(dd, J = 8.1, 1.2 Hz, 1H), 7.52 – 7.44 (m, 5H), 7.44 – 7.38 (m, 2H), 7.20 –7.15 (m, 1H), 7.15 – 7.10 (m, 2H), 7.06 (td, J = 7.9, 7.4, 1.2 Hz, 1H), 6.75(dd, J = 8.3, 1.1 Hz, 1H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 147.27, 142.07,132.92, 132.79, 132.55, 131.21, 130.50, 129.95, 129.75, 129.51, 128.47,128.16, 125.86, 124.67, 124.30, 113.45. HRMS (ESI-FT) m / z: [M+H] + Calcd forC 21 H 13 N2SClH 361.0560; Found 361.0565.

[0078] Example 11

[0079] The preparation method of 7-methyl-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0080] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-diphenyl-2H-azirine, 0.5 mmol of 2-bromo-1-isothiocyanato-4-methylbenzene, and 0.5 mmol of cesium carbonate to a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 7-methyl-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 84%.

[0081] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 7.1 Hz, 6H), 7.40 – 7.37 (m, 1H), 7.19 – 7.08 (m, 4H), 6.86 (dd, J = 8.3, 1.7 Hz, 1H), 6.64 (d, J = 8.4 Hz, 1H), 2.31 (s, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 146.95, 142.79, 134.63, 134.06, 131.30, 130.94, 130.56, 130.31, 129.46, 129.32, 128.27, 126.94, 126.76, 124.31, 124.25, 113.06, 21.24. HRMS(ESI-FT) m / z: [M+H] + Calcd for C 22 H 16 N2SH 341.1106; Found 341.1113.

[0082] Example 12

[0083] The preparation method of 3-(4-ethylphenyl)-7-methyl-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0084] Add 2 mL of dimethyl sulfoxide, 0.5 mmol of 3-(4-ethylphenyl)-2-phenyl-2H-azirine, 0.5 mmol of 2-bromo-1-isothiocyanato-4-methylbenzene, and 0.5 mmol of cesium carbonate to a 10 mL dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 h. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 min. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 3-(4-ethylphenyl)-7-methyl-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 83%.

[0085] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.52 –7.47 (m, 2H), 7.38 – 7.33 (m, 3H), 7.28 (d, J = 8.0 Hz, 2H), 7.18 – 7.11 (m,2H), 7.11 – 7.06 (m, 1H), 6.84 (dd, J = 8.5, 1.7 Hz, 1H), 6.64 (d, J = 8.4Hz, 1H), 2.71 (q, J = 7.6 Hz, 2H), 2.28 (s, 3H), 1.27 (t, J = 7.6 Hz, 3H). 13 C{ 1 H} NMR (100 MHz, CDCl3) δ 146.80, 145.62, 142.79, 134.49, 134.33, 131.14,131.02, 130.54, 128.77, 128.23, 127.41, 126.91, 126.82, 126.72, 124.41,124.26, 113.11, 28.80, 21.24, 15.31. HRMS (ESI-FT) m / z: [M+H] + Calcd forC 24 H 20 N2SH 369.1419; Found 369.1426.

[0086] Example 13

[0087] Preparation method of 3-(4-methoxyphenyl)-7-methyl-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0088] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-methoxyphenyl)-2-phenyl-2H-azirine, 0.5 mmol of 2-bromo-1-isothiocyanato-4-methylbenzene, and 0.5 mmol of cesium carbonate into a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine. Dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 10:1) as the eluent to obtain the final product 3-(4-methoxyphenyl)-7-methyl-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 80%.

[0089] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.53 –7.48 (m, 2H), 7.38 – 7.34 (m, 3H), 7.19 – 7.12 (m, 2H), 7.12 – 7.06 (m, 1H),7.01 – 6.96 (m, 2H), 6.87 – 6.83 (m, 1H), 6.65 (d, J = 8.3 Hz, 1H), 3.84 (d,J = 1.1 Hz, 3H), 2.29 (s, 3H). 13 C{ 1 H} NMR (100 MHz, CDCl3) δ 160.39, 146.70,142.84, 134.48, 134.37, 132.55, 131.02, 130.54, 128.24, 126.80, 126.72,124.28, 124.04, 122.29, 114.76, 113.01, 55.39, 21.24. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 23 H 18 N2OSH 371.1212; Found 371.1218.

[0090] Example 14

[0091] Preparation method of 7-methoxy-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0092] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-diphenyl-2H-azirine, 0.5 mmol of 2-bromo-1-isothiocyanato-4-methoxybenzene, and 0.5 mmol of cesium carbonate into a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 10:1) as the eluent to obtain the final product 7-methoxy-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 81%.

[0093] The nuclear magnetic resonance and high-resolution spectrum data of the above product (its single crystal spectrum, nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum are as Figures 1 to 3 shown) are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.51 – 7.43 (m, 7H), 7.21 – 7.06(m, 4H), 6.69 – 6.55 (m, 2H), 3.71 (s, 3H). 13 C{ 1 H} NMR (100 MHz, CDCl3) δ156.77, 146.50, 142.73, 134.28, 131.81, 131.28, 130.31, 129.43, 129.35,128.26, 127.22, 126.87, 126.86, 124.20, 113.91, 112.80, 108.67, 55.84. HRMS(ESI-FT) m / z: [M+H] + Calcd for C 24 H 20 N2SH 369.1419; Found 369.1426.

[0094] Example 15

[0095] Preparation method of 6-methyl-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0096] In a 10 ml dry round-bottom flask, 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-diphenyl-2H-azirine, 0.5 mmol of 1-bromo-2-isothiocyanato-4-methylbenzene, and 0.5 mmol of cesium carbonate were added. The reaction mixture was heated and stirred at 100 °C for 16 hours. After the reaction was completed, it was quenched with water, diluted with dichloromethane, and stirred for 30 minutes. Then, liquid separation by extraction was carried out. The aqueous phase was washed with dichloromethane 2-3 times, the organic phase was washed with saturated brine, the obtained organic phase was dried over anhydrous sodium sulfate, then filtered, concentrated under reduced pressure, and further separated by column chromatography using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 6-methyl-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 78%.

[0097] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.53 –7.42 (m, 8H), 7.19 – 7.07 (m, 3H), 6.98 (dd, J = 8.1, 1.7 Hz, 1H), 6.54 (d, J= 1.6 Hz, 1H), 2.15 (s, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 147.57, 143.01,136.04, 134.12, 133.12, 131.35, 130.35, 129.50, 129.27, 128.27, 127.20,126.97, 125.63, 124.27, 123.79, 114.01, 21.62. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 22 H 16 N2SH 341.1106; Found 341.1113.

[0098] Example 16

[0099] The preparation method of 6-methyl-2-phenyl-3-(p-tolyl)benzo[d]imidazo[2,1-b]thiazole is as follows:

[0100] In a 10 ml dry round-bottom flask, 2 ml of dimethyl sulfoxide, 0.5 mmol of 2-phenyl-3-(p-tolyl)-2H-azirine, 0.5 mmol of 1-bromo-2-isothiocyanato-4-methylbenzene, and 0.5 mmol of cesium carbonate were added. The reaction mixture was heated and stirred at 100 °C for 16 hours. After the reaction was completed, it was quenched with water, diluted with dichloromethane, and stirred for 30 minutes. Then, liquid separation by extraction was carried out. The aqueous phase was washed with dichloromethane 2 - 3 times, the organic phase was washed with saturated brine, the obtained organic phase was dried over anhydrous sodium sulfate, then filtered, concentrated under reduced pressure, and further separated by column chromatography using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 6-methyl-2-phenyl-3-(p-tolyl)benzo[d]imidazo[2,1-b]thiazole with a yield of 60%.

[0101] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.52 –7.44 (m, 5H), 7.36 (d, J = 8.1 Hz, 2H), 7.29 (d, J = 7.8 Hz, 2H), 7.21 – 7.09(m, 6H), 7.00 (qd, J = 7.9, 7.1, 2.5 Hz, 2H), 6.59 (d, J = 20.9 Hz, 1H), 2.45(s, 3H), 2.18 (s, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 142.70, 139.50, 136.05,131.13, 130.00, 128.34, 128.25, 127.21, 126.95, 125.66, 123.77, 114.10,21.66, 21.61. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 23 H 18 N2SH 355.1263; Found355.1266.

[0102] Example 17

[0103] The preparation method of 3-(4-methoxyphenyl)-6-methyl-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0104] In a 10 ml dry round-bottom flask, 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-methoxyphenyl)-2-phenyl-2H-azirine, 0.5 mmol of 1-bromo-2-isothiocyanato-4-methylbenzene, and 0.5 mmol of cesium carbonate were added. The reaction mixture was heated and stirred at 100 °C for 16 hours. After the reaction was completed, the reaction was quenched with water, diluted with dichloromethane, and stirred for 30 minutes. Then, liquid-liquid extraction was carried out. The aqueous phase was washed with dichloromethane 2-3 times, and the organic phase was washed with saturated brine. The obtained organic phase was dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then separated by column chromatography using petroleum ether / ethyl acetate (v / v = 10:1) as the eluent to obtain the final product 3-(4-methoxyphenyl)-6-methyl-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 76%.

[0105] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.53 –7.47 (m, 2H), 7.43 (d, J = 8.1 Hz, 1H), 7.39 – 7.33 (m, 2H), 7.15 (dd, J =8.2, 6.4 Hz, 2H), 7.12 – 7.06 (m, 1H), 6.98 (dd, J = 11.0, 8.5 Hz, 3H), 6.61(d, J = 1.6 Hz, 1H), 3.85 (s, 3H), 2.16 (s, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3)δ 160.42, 147.34, 143.08, 136.00, 134.35, 133.22, 132.59, 128.24, 127.18,126.87, 126.83, 125.56, 124.07, 123.77, 122.29, 114.70, 113.96, 55.43, 21.69.HRMS (ESI-FT) m / z: [M+H] + Calcd for C 23 H 18 N2OSH 371.1212; Found 371.1218.

[0106] Example 18

[0107] The preparation method of 7-chloro-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0108] In a 10 ml dry round-bottom flask, 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-diphenyl-2H-azirine, 0.5 mmol of 2-bromo-4-chloro-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate were added. The reaction mixture was heated and stirred at 100 °C for 16 hours. After the reaction was completed, the reaction was quenched with water, diluted with dichloromethane, and stirred for 30 minutes. The layers were separated by extraction. The aqueous phase was washed with dichloromethane 2-3 times, and the organic phase was washed with saturated brine. The obtained organic phase was dried over anhydrous sodium sulfate, then filtered, concentrated under reduced pressure, and further separated by column chromatography using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 7-chloro-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 83%.

[0109] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 2.1 Hz, 1H), 7.49 (ddd, J = 11.6, 5.1, 2.6 Hz, 5H), 7.32 (d, J = 2.3 Hz, 1H), 7.14 (dd, J = 12.0, 7.2 Hz, 2H), 7.03 (dd, J = 8.8, 2.1 Hz, 1H), 6.98 (dd, J = 8.5, 2.4 Hz, 1H), 6.66 (d, J = 8.8 Hz, 1H), 6.60 (d, J = 8.5 Hz, 1H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 146.80, 142.87, 133.74, 131.83, 131.23, 130.05, 129.75, 129.51, 128.34, 127.22, 126.97, 126.20, 123.95, 116.20, 114.02, 109.14. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 21 H 13 N2SClH 361.0560; Found 361.0565.

[0110] Example 19

[0111] The preparation method of 7-chloro-3-(4-methoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0112] In a 10 ml dry round-bottom flask, 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-ethylphenyl)-2-phenyl-2H-azirine, 0.5 mmol of 2-bromo-4-chloro-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate were added. The reaction mixture was heated and stirred at 100 °C for 16 hours. After the reaction was completed, the reaction was quenched with water, diluted with dichloromethane, and stirred for 30 minutes. Then, liquid separation by extraction was carried out. The aqueous phase was washed with dichloromethane 2 - 3 times, and the organic phase was washed with saturated brine. The obtained organic phase was dried over anhydrous sodium sulfate, then filtered, concentrated under reduced pressure, and further separated by column chromatography using petroleum ether / ethyl acetate (v / v = 10:1) as the eluent to obtain the final product 7-chloro-3-(4-methoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 82%.

[0113] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.91 –7.83 (m, 1H), 7.54 (d, J = 2.1 Hz, 1H), 7.38 – 7.33 (m, 2H), 7.20 – 7.07 (m,3H), 7.05 – 6.97 (m, 3H), 6.89 (dd, J = 8.9, 2.0 Hz, 1H), 6.68 (d, J = 8.8Hz, 1H), 3.84 (s, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 160.58, 146.54, 143.29,134.74, 132.50, 131.98, 129.92, 128.98, 128.32, 127.08, 126.83, 126.15,123.90, 121.68, 114.95, 114.39, 114.00, 55.42. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 22 H 15 N2SOClH 391.0666; Found 391.0671.

[0114] Example 20

[0115] A preparation method of 7-chloro-3-(4-ethylphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0116] In a 10 ml dry round-bottom flask, add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-methoxyphenyl)-2-phenyl-2H-azirine, 0.5 mmol of 2-bromo-4-chloro-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 7-chloro-3-(4-ethylphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 64%.

[0117] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.49(dd, J = 8.3, 1.5 Hz, 2H), 7.35 (d, J = 8.1 Hz, 2H), 7.19 – 7.12 (m, 2H),7.02 (dd, J = 8.7, 2.1 Hz, 1H), 6.96 (dd, J = 8.5, 2.4 Hz, 2H), 6.66 (d, J =8.7 Hz, 1H), 6.57 (d, J = 8.5 Hz, 2H), 2.72 (q, J = 7.6 Hz, 2H), 1.27 (t, J =7.6 Hz, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 146.64, 145.94, 142.90, 134.01,131.81, 131.07, 129.90, 128.95, 128.34, 128.30, 127.09, 126.94, 126.15,123.87, 116.21, 114.07, 109.14, 28.80, 15.28. HRMS (ESI-FT) m / z: [M+H] + Calcdfor C 23 H 17 N2SClH 389.0873; Found 389.0877.

[0118] Example 21

[0119] Preparation method of 7-chloro-3-(2,5-dimethoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0120] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(2,5-dimethoxyphenyl)-2-phenyl-2H-azirine, 0.5 mmol of 2-bromo-4-chloro-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate into a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine. Dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and then perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 10:1) as the eluent to obtain the final product 7-chloro-3-(2,5-dimethoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 60%.

[0121] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.54(td, J = 8.6, 1.3 Hz, 3H), 7.20 – 7.04 (m, 4H), 7.03 – 6.93 (m, 2H), 6.85 (d,J = 3.0 Hz, 1H), 6.77 (dd, J = 8.1, 1.3 Hz, 1H), 3.63 (s, 3H), 3.54 (s, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 152.82, 151.71, 146.25, 142.42, 133.23,132.24, 129.32, 127.20, 125.85, 125.71, 124.74, 123.29, 122.94, 119.51,118.63, 117.01, 115.48, 112.19, 111.62, 55.05, 54.78. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 23 H 17 N2O2SH 421.0772; Found 421.0774.

[0122] Example 22

[0123] Preparation method of 7-chloro-3-(4-fluorophenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0124] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-fluorophenyl)-2-phenyl-2H-azirine, 0.5 mmol of 2-bromo-4-chloro-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate into a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 7-chloro-3-(4-fluorophenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 61%.

[0125] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.33(d, J = 8.8 Hz, 1H), 7.58 – 7.49 (m, 6H), 7.31 – 7.24 (m, 4H), 7.18 (s, 1H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 150.24, 147.49, 142.85, 138.23, 136.05,132.13, 131.84, 129.80, 128.75, 128.43, 128.36, 126.95, 123.00, 121.14,120.83, 120.59, 116.22, 115.46, 115.24, 113.23, 109.15. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 21 H 12 N2SFH 379.0466; Found 379.0471.

[0126] Example 23

[0127] Preparation method of 7-bromo-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0128] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-diphenyl-2H-azirine, 0.5 mmol of 2,4-dibromo-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate to a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 7-bromo-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 65%.

[0129] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.72(d, J = 1.9 Hz, 1H), 7.47 (d, J = 1.7 Hz, 2H), 7.44 (d, J = 2.3 Hz, 2H), 7.20– 7.13 (m, 3H), 7.10 (dd, J = 8.6, 2.2 Hz, 2H), 6.58 (dd, J = 18.7, 8.6 Hz,3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 146.72, 143.31, 134.45, 131.22, 131.16,129.77, 129.51, 129.01, 128.35, 127.25, 126.97, 126.76, 124.37, 116.70,114.41, 109.55. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 21 H 13 N2SBrH 407.0035;Found 407.0045.

[0130] Example 24

[0131] The preparation method of 7-bromo-3-(4-ethylphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0132] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-ethylphenyl)-2-phenyl-2H-azirine, 0.5 mmol of 2,4-dibromo-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate to a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 7-bromo-3-(4-ethylphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 78%.

[0133] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 2.0 Hz, 1H), 7.50 – 7.46 (m, 2H), 7.34 (d, J = 8.1 Hz, 2H), 7.29 (d, J = 7.9 Hz, 2H), 7.21 – 7.05 (m, 4H), 6.61 (d, J = 8.7 Hz, 1H), 2.72 (q, J = 7.6 Hz, 2H), 1.27 (t, J = 7.6 Hz, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 146.55, 145.95, 143.39, 134.45, 134.00, 132.31, 132.03, 131.07, 128.95, 128.29, 127.09, 126.93, 126.67, 124.52, 117.14, 116.70, 114.44, 28.80, 15.28. HRMS(ESI-FT) m / z: [M+H] + Calcd for C 23 H 17 N2SBrH 435.0348; Found 435.0350.

[0134] Example 25

[0135] The preparation method of 7-bromo-3-(4-methoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0136] In a 10 ml dry round-bottom flask, add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-methoxyphenyl)-2-phenyl-2H-azirine, 0.5 mmol of 2,4-dibromo-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate. Heat the reaction mixture with stirring at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 10:1) as the eluent to obtain the final product 7-bromo-3-(4-methoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 76%.

[0137] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.67(d, J = 1.9 Hz, 1H), 7.52 – 7.46 (m, 2H), 7.37 – 7.31 (m, 2H), 7.18 – 7.07(m, 4H), 6.98 (d, J = 8.6 Hz, 2H), 6.61 (dd, J = 8.7, 1.2 Hz, 1H), 3.83 (d, J= 1.3 Hz, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 160.57, 146.45, 143.39, 134.01,132.50, 132.03, 129.93, 128.92, 128.31, 127.07, 126.82, 126.69, 124.16,121.70, 117.12, 114.94, 114.36, 55.42. HRMS (ESI-FT) m / z: [M+H] + Calcd forC 22 H 15 N2OSBrH 437.0141; Found 437.0137.

[0138] Example 26

[0139] The preparation method of 7-bromo-3-phenyl-2-(p-tolyl)benzo[d]imidazo[2,1-b]thiazole is as follows:

[0140] In a 10 ml dry round-bottom flask, add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-phenyl-2-(p-tolyl)-2H-azirine, 0.5 mmol of 2,4-dibromo-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate. Heat the reaction mixture with stirring at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 7-bromo-3-phenyl-2-(p-tolyl)benzo[d]imidazo[2,1-b]thiazole with a yield of 77%.

[0141] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.69(d, J = 2.0 Hz, 1H), 7.50 – 7.41 (m, 7H), 7.38 – 7.34 (m, 2H), 7.18 – 7.13(m, 1H), 7.10 (dd, J = 8.6, 2.2 Hz, 3H), 6.97 (d, J = 8.0 Hz, 2H), 6.57 (dd,J = 20.4, 8.6 Hz, 4H), 2.21 (s, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 146.63,143.62, 143.30, 136.97, 134.46, 131.25, 131.18, 129.47, 129.08, 128.94,126.88, 126.72, 117.13, 116.72, 114.33, 109.57, 21.24. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 22 H 15 N2SBrH 421.0192; Found 421.0191.

[0142] Example 27

[0143] The preparation method of 7-bromo-2,3-bis(p-tolyl)benzo[d]imidazo[2,1-b]thiazole is as follows:

[0144] In a 10 ml dry round-bottom flask, 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-bis(p-tolyl)-2H-azirine, 0.5 mmol of 2,4-dibromo-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate were added. The reaction mixture was heated and stirred at 100 °C for 16 hours. After the reaction was completed, it was quenched with water, diluted with dichloromethane, and stirred for 30 minutes. Then, liquid separation by extraction was carried out. The aqueous phase was washed with dichloromethane 2-3 times, and the organic phase was washed with saturated brine. The obtained organic phase was dried over anhydrous sodium sulfate, then filtered, concentrated under reduced pressure, and further separated by column chromatography using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 7-bromo-2,3-bis(p-tolyl)benzo[d]imidazo[2,1-b]thiazole with a yield of 75%.

[0145] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.57(d, J = 2.1 Hz, 1H), 7.55 – 7.49 (m, 2H), 7.22 – 7.10 (m, 3H), 7.04 (ddd, J =15.0, 8.9, 2.5 Hz, 2H), 6.97 (d, J = 9.0 Hz, 1H), 6.84 (d, J = 3.0 Hz, 1H),6.69 (d, J = 8.8 Hz, 1H), 3.65 (s, 3H), 3.57 (s, 3H). 13 C { 1 H} NMR (100 MHz,CDCl3) δ 152.90, 151.58, 145.93, 142.65, 132.96, 130.79, 128.73, 127.25,126.04, 125.74, 125.14, 122.62, 118.17, 116.97, 115.65, 112.86, 111.62,55.06, 54.81. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 23 H 17 N2SBrH 435.0348; Found435.0350.

[0146] Example 28

[0147] The preparation method of 7-bromo-2-(4-chlorophenyl)-3-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0148] In a 10 ml dry round-bottom flask, 2 ml of dimethyl sulfoxide, 0.5 mmol of 2-(4-chlorophenyl)-3-phenyl-2H-azirine, 0.5 mmol of 2,4-dibromo-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate were added. The reaction mixture was heated and stirred at 100 °C for 16 hours. After the reaction was completed, the reaction was quenched with water, diluted with dichloromethane, and stirred for 30 minutes. Then, liquid separation by extraction was carried out. The aqueous phase was washed with dichloromethane 2-3 times, and the organic phase was washed with saturated brine. The obtained organic phase was dried over anhydrous sodium sulfate, then filtered, concentrated under reduced pressure, and further separated by column chromatography using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 7-bromo-2-(4-chlorophenyl)-3-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 67%.

[0149] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 8.8 Hz, 1H), 7.71 (dd, J = 7.8, 1.9 Hz, 3H), 7.64 (d, J = 2.2 Hz, 1H), 7.44 (d, J = 2.3 Hz, 7H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 149.42, 145.82, 142.22, 133.40, 130.11, 130.04, 128.89, 128.58, 128.00, 127.47, 127.09, 125.73, 122.35, 115.64, 113.33, 108.52. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 21 H 12 N2SClBrH 440.9642; Found 440.9644.

[0150] Example 29

[0151] The preparation method of 7-bromo-2,3-bis(p-tolyl)benzo[d]imidazo[2,1-b]thiazole is as follows:

[0152] In a 10 ml dry round-bottom flask, add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-phenyl-2-(2-thienyl)-2H-azirine, 0.5 mmol of 2,4-dibromo-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 7-bromo-2,3-bis(p-tolyl)benzo[d]imidazo[2,1-b]thiazole with a yield of 70%.

[0153] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.72(d, J = 2.0 Hz, 1H), 7.62 – 7.56 (m, 3H), 7.25 – 7.13 (m, 6H), 6.62 (d, J =8.6 Hz, 1H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 143.29, 134.47, 133.46, 132.17,131.47, 131.18, 129.90, 129.66, 129.26, 128.42, 128.23, 127.61, 126.89,126.73, 116.72, 114.34, 109.58. HRMS (ESI-FT) m / z: [M+H] + Calcd forC 19 H 11 N2S2BrH 412.9599; Found 412.9603.

[0154] Example 30

[0155] A preparation method of 7-fluoro-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0156] In a 10 ml dry round-bottom flask, add 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-diphenyl-2H-azirine, 0.5 mmol of 2-bromo-4-fluoro-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 7-fluoro-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 80%.

[0157] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.47(td, J = 5.3, 4.7, 2.8 Hz, 6H), 7.29 (dd, J = 8.0, 2.6 Hz, 1H), 7.18 – 7.12(m, 2H), 7.12 – 7.09 (m, 1H), 6.76 (tdd, J = 8.9, 6.6, 2.7 Hz, 1H), 6.67 (dd,J = 9.0, 4.5 Hz, 1H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ 160.61, 158.17, 146.74,143.16, 133.94, 131.98, 131.88, 131.25, 129.94, 129.68, 129.49, 128.32,127.11, 126.94, 124.34, 119.06, 115.96, 115.89, 114.10, 114.02, 113.48,113.24, 111.41, 111.14. 19 F NMR (376 MHz, CDCl3) δ -116.13, -118.86, -125.26.HRMS (ESI-FT) m / z: [M+H] + Calcd for C 21 H 13 N2SFH 345.0856; Found 345.0863.

[0158] Example 31

[0159] Preparation method of 3-(4-ethylphenyl)-7-fluoro-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0160] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-ethylphenyl)-2-phenyl-2H-azirine, 0.5 mmol of 2-bromo-4-fluoro-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate into a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine. Dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 3-(4-ethylphenyl)-7-fluoro-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 74%.

[0161] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.52 –7.48 (m, 2H), 7.37 (d, J = 8.1 Hz, 2H), 7.34 – 7.30 (m, 3H), 7.14 (dd, J =15.1, 7.4 Hz, 2H), 6.84 – 6.75 (m, 2H), 6.72 (dd, J = 9.1, 4.5 Hz, 1H), 2.74(q, J = 7.6 Hz, 2H), 1.29 (t, J = 7.6 Hz, 3H). 13 C { 1 H} NMR (100 MHz, CDCl3) δ160.62, 158.18, 146.54, 145.94, 142.85, 133.88, 131.96, 131.87, 131.10,129.62, 128.95, 128.30, 127.07, 126.89, 126.86, 124.50, 119.33, 119.08,115.96, 113.50, 113.26, 111.36, 111.09, 28.79, 15.25. 19 F NMR (376 MHz, CDCl3)δ -107.15, -116.20, -118.80, -125.27. HRMS (ESI-FT) m / z: [M+H] +Calcd for C 23 H 17 N2SFH 373.1169; Found 373.1175.

[0162] Example 32

[0163] Preparation method of 7-fluoro-3-(4-methoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0164] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-methoxyphenyl)-2-phenyl-2H-azirine, 0.5 mmol of 2-bromo-4-fluoro-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate into a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and then perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 10:1) as the eluent to obtain the final product 7-fluoro-3-(4-methoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 79%.

[0165] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.53 –7.47 (m, 2H), 7.39 – 7.34 (m, 2H), 7.29 (dd, J = 8.1, 2.5 Hz, 1H), 7.16 (dd,J = 7.3, 5.8 Hz, 2H), 7.12 – 7.06 (m, 1H), 7.00 (d, J = 8.3 Hz, 2H), 6.84 –6.74 (m, 1H), 6.71 (dd, J = 9.1, 4.6 Hz, 1H), 3.84 (d, J = 1.3 Hz, 3H). 13 C{ 11H NMR (100 MHz, CDCl3) δ 160.54, 158.14, 146.46, 143.05, 134.09, 132.53, 131.96, 131.86, 129.64, 128.30, 126.99, 126.78, 124.14, 121.78, 114.93, 114.09, 114.00, 113.45, 113.21, 111.37, 111.09, 55.41. 19 19F NMR (376 MHz, CDCl3) δ -116.25. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 22 H 15 N2OSFH 375.0961; Found 375.0968.

[0166] Example 33

[0167] Preparation method of 7-fluoro-2,3-bis(p-tolyl)benzo[d]imidazo[2,1-b]thiazole is as follows:

[0168] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-bis(p-tolyl)-2H-azirine, 0.5 mmol of 2-bromo-4-fluoro-1-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate into a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 7-fluoro-2,3-bis(p-tolyl)benzo[d]imidazo[2,1-b]thiazole with a yield of 80%.

[0169] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 1H NMR (400 MHz, CDCl3) δ 7.40 –7.34 (m, 2H), 7.32 (d, J = 8.1 Hz, 2H), 7.30 – 7.23 (m, 3H), 6.96 (d, J = 8.0 Hz, 2H), 6.80 – 6.68 (m, 2H), 2.41 (s, 3H), 2.20 (s, 3H). 13 13C { 11H NMR (100 MHz, CDCl3) δ 160.52, 158.09, 146.44, 143.19, 139.57, 136.72, 131.92, 131.81, 131.25, 131.08, 130.18, 129.65, 129.01, 126.93, 126.78, 124.00, 114.10, 114.01, 113.37, 113.14, 111.32, 111.05, 21.60, 21.21. 19 19F NMR (376 MHz, CDCl3) δ -116.42, -118.91, -125.26. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 23 H 17 N2SFH373.1169; Found 373.1175.

[0170] Example 34

[0171] Preparation method of 7-nitro-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0172] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-diphenyl-2H-azirine, 0.5 mmol of 2-bromo-1-isothiocyanato-4-nitrobenzene, and 0.5 mmol of cesium carbonate into a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and then perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 10:1) as the eluent to obtain the final product 7-nitro-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 65%.

[0173] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 1H NMR (400 MHz, CDCl3 ) δ 8.78 (d, J = 9.2 Hz, 1H), 8.50 (d, J = 9.2 Hz, 2H), 8.18 (td, J = 9.0, 2.6 Hz, 3H), 7.52 – 7.42 (m, 6H), 7.18 (s, 1H). 13 13C{ 11H NMR (100 MHz, CDCl3) δ 146.16, 143.17, 141.37, 134.29, 133.60, 133.04, 131.29, 129.67, 129.26, 128.93, 128.42, 127.26, 124.82, 124.39, 116.11. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 21 H 13 N2O3SH 372.0725; Found 371.0730.

[0174] Example 35

[0175] Preparation method of 6-chloro-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0176] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 2,3-diphenyl-2H-azirine, 0.5 mmol of 1-bromo-4-chloro-2-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate into a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 30:1) as the eluent to obtain the final product 6-chloro-2,3-diphenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 78%.

[0177] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 1H NMR (400 MHz, CDCl3) δ 7.56 – 7.42 (m, 8H), 7.21 – 7.09 (m, 5H), 6.72 (d, J = 2.0 Hz, 1H). 13 13C{ 1 1H} NMR (100 MHz, CDCl3) δ 147.55, 143.52, 133.77, 133.58, 131.72, 131.16, 129.88, 129.69, 129.55, 128.34, 127.24, 127.00, 124.89, 124.74, 124.35, 113.81. HRMS (ESI-FT) m / z: [M+H] +Calcd for C 24 H 20 N2SH 369.1419; Found 369.1426.

[0178] Example 36

[0179] Preparation method of 6-chloro-3-(4-methoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole is as follows:

[0180] Add 2 ml of dimethyl sulfoxide, 0.5 mmol of 3-(4-methoxyphenyl)-2-phenyl-2H-azirine, 0.5 mmol of 1-bromo-4-chloro-2-isothiocyanatobenzene, and 0.5 mmol of cesium carbonate into a 10 ml dry round-bottom flask. Heat and stir the reaction mixture at 100 °C for 16 hours. After the reaction is completed, quench with water, dilute with dichloromethane, and stir for 30 minutes. Extract and separate the layers. Wash the aqueous phase with dichloromethane 2 - 3 times, wash the organic phase with saturated brine, dry the obtained organic phase with anhydrous sodium sulfate, then filter, concentrate under reduced pressure, and perform column chromatography separation using petroleum ether / ethyl acetate (v / v = 10:1) as the eluent to obtain the final product 6-chloro-3-(4-methoxyphenyl)-2-phenylbenzo[d]imidazo[2,1-b]thiazole with a yield of 82%.

[0181] The nuclear magnetic resonance and high-resolution spectrum data of the above product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.50(dd, J = 8.5, 1.6 Hz, 3H), 7.40 – 7.33 (m, 2H), 7.22 – 7.08 (m, 4H), 7.07 –6.99 (m, 2H), 6.79 (d, J = 2.0 Hz, 1H), 3.87 (s, 3H). 13 C{ 1 H} NMR (100 MHz,CDCl3) δ 160.66, 147.29, 143.49, 133.93, 133.67, 132.44, 131.70, 128.80,128.32, 127.12, 126.90, 124.86, 124.68, 124.16, 121.51, 114.99, 113.76,55.47. HRMS (ESI-FT) m / z: [M+H] + Calcd for C 22 H 15 N2SOClH 391.0666; Found391.0671.

[0182] Those skilled in the art should understand that those skilled in the art can implement variant examples by combining the prior art and the above embodiments, which will not be elaborated herein. Such variant examples do not affect the substantial content of the present invention and will not be elaborated herein.

[0183] The preferred embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the above specific implementation manners, and the devices and structures not described in detail should be understood to be implemented in a common manner in the art; any person skilled in the art can, without departing from the scope of the technical solution of the present invention, make many possible changes and modifications to the technical solution of the present invention by using the methods and technical contents disclosed above, or modify it into an equivalent embodiment with equivalent changes, which does not affect the substantial content of the present invention. Therefore, any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of protection of the technical solution of the present invention.

Claims

1. A method for synthesizing benzo[d]imidazole[2,1-b]thiazole, characterized in that: 2H-aziridine, o-bromoaryl isothiocyanate, an organic solvent and a base are reacted under stirring. After the reaction is completed, the liquid is extracted, washed, dried, concentrated and separated by column chromatography to obtain benzo[d]imidazole[2,1-b]thiazole.

2. A method for synthesizing benzo[d]imidazole[2,1-b]thiazole according to claim 1, characterized in that: The reaction temperature is 100°C and the reaction time is 16h; After the reaction is completed, water is added to quench, dichloromethane is added to dilute, and the mixture is stirred; The aqueous phase obtained by extraction and separation was washed with dichloromethane 2 to 3 times, and the organic phase obtained by extraction and separation was washed with saturated brine.

3. A method for synthesizing benzo[d]imidazole[2,1-b]thiazole according to claim 1, characterized in that: The 2H-azapropene is at least one of 2,3-diphenyl-2H-azapropene, 2-phenyl-3-p-tolyl-2H-azapropene, 3-(4-ethylphenyl)-2-phenyl-2H-azapropene, 3-(4-methoxyphenyl)-2-phenyl-2H-azapropene, 3-(4-fluorophenyl)-2-phenyl-2H-azapropene, 3-(4-chlorophenyl)-2-phenyl-2H-azapropene, 3-(4-bromophenyl)-2-phenyl-2H-azapropene, 2-phenyl-3-(5,6,7,8-tetrahydronaphthalene-2-yl)-2H-azapropene, 3-phenyl-2-p-tolyl-2H-azapropene and 2-(4-chlorophenyl)-3-phenyl-2H-azapropene.

4. A method for synthesizing benzo[d]imidazole[2,1-b]thiazole according to claim 1, characterized in that: The ortho-bromoaryl isothiocyanate is at least one of 1-bromo-2-isothiocyanate phenyl ester, 2-bromo-4-fluoro-1-isothiocyanate phenyl ester, 2,4-dibromo-1-isothiocyanate phenyl ester, 2-bromo-1-isothiocyanate-4-methylphenyl ester, 2-bromo-4-chloro-1-isothiocyanate phenyl ester, 1-bromo-4-chloro-2-isothiocyanate phenyl ester, 1-bromo-2-isothiocyanate-4-methylphenyl ester, 2-bromo-1-isothiocyanate-4-methoxyphenyl ester, 1-chloro-2-isothiocyanate phenyl ester and 2-bromo-1-isothiocyanate-4-nitrophenyl ester.

5. A method for synthesizing benzo[d]imidazole[2,1-b]thiazole according to claim 1, characterized in that: The organic solvent is at least one of N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dichloromethane, tetrahydrofuran and acetonitrile.

6. A method for synthesizing benzo[d]imidazole[2,1-b]thiazole according to claim 1, characterized in that: The base is at least one of cesium carbonate, triethylamine, sodium hydride, sodium bicarbonate, potassium hydroxide, 1,4-diazabicyclo[2.2.2]octane and 1,8-diazabicycloundec-7-ene.

7. A method for synthesizing benzo[d]imidazole[2,1-b]thiazole according to claim 1, characterized in that: The molar ratio of the 2H-aziridine, o-bromoaryl isothiocyanate and the base is 1:1:

1.

8. A method for synthesizing benzo[d]imidazole[2,1-b]thiazole according to claim 2, characterized in that: The organic phase obtained by extraction and separation was washed and then dried over anhydrous sodium sulfate.

9. A method for synthesizing benzo[d]imidazole[2,1-b]thiazole according to claim 1, characterized in that: The eluent used in the column chromatography separation is a mixture of petroleum ether and ethyl acetate.

10. A method for synthesizing benzo[d]imidazole[2,1-b]thiazole according to claim 9, characterized in that: The volume ratio of petroleum ether to ethyl acetate in the eluent is 10:1 to 30:1.

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