Preparation method of sulfo-styryl pyrrolo [1, 2-a] quinoxaline and derivative thereof

Abstract

The invention relates to the technical field of organic synthesis, in particular to a preparation method of sulfo-styryl pyrrolo [1, 2-a] quinoxaline and derivatives thereof, which comprises the following steps: mixing aryl ethynyl pyrrolo [1, 2-a] quinoxaline, arylthiophenol, organic alkali and a first solvent for reaction, cooling the reaction liquid to room temperature after the reaction is finished, and then separating and purifying, thereby obtaining the sulfo-styryl pyrrolo [1, 2-a] quinoxaline derivative. Or mixing one of diaryl diselenide or arylthiophenol with a second solvent, stirring at room temperature for 5-15 minutes, then adding aryl ethynyl pyrrolo [1, 2-a] quinoxaline and an oxidizing agent, stirring at room temperature for 15-30 minutes, after the reaction is finished, quenching the reaction liquid, and then extracting, separating and purifying to obtain the thiostyryl pyrrolo [1, 2-a] quinoxaline and the derivative of the thiostyryl pyrrolo [1, 2-a] quinoxaline. According to the invention, the research limitation of pyrroloquinoxaline C1 / C3 site functionalization is broken through, a modification site is expanded to an alkynyl alpha-H site for the first time, and a new way is opened up for the design of novel functional molecules and the development of high-performance polymers.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and more specifically, to a preparation method of thienylvinyl pyrrolo[1,2-a]quinoxaline and its derivatives. Background Art

[0002] The rapid development of materials science has greatly promoted the practical applications of organic compounds, especially achieving remarkable breakthroughs in the field of functional materials. Among them, vinyl monomers containing heteroatom bonds have attracted much attention due to their unique chemical properties. Such monomers can be efficiently transformed into functional polymers through various well-established polymerization routes, providing broad space for material design. As a class of high-performance new materials, heteroatom-functionalized polymers exhibit great application potential in multiple fields, including high-performance engineering plastics, optical and optoelectronic devices, network polymers, fuel cell membranes, proton-conducting electrolytes, and photochemical materials. Notably, sulfur-containing polymers show unique advantages in the biomedical field, especially as biomembrane materials. The introduction of sulfur atoms provides an important means to regulate the physical and chemical properties of polymers, such as significantly enhancing the refractive index of materials, improving elastic behavior, and enhancing thermal stability. From the perspective of synthetic methodology, the atom-economic addition reaction of thiols and alkynes provides an extremely attractive route for the efficient preparation of vinyl sulfides. This strategy not only conforms to the principles of green chemistry but also lays an important foundation for the precise synthesis of functional polymers.

[0003] Pyrrolo[1,2-a]quinoxaline and its derivatives, as nitrogen heterocyclic compounds with unique rigid skeletons and biological activities, have attracted attention in recent years due to their extensive application values. In the field of drug research and development, the pharmacological activities can be significantly enhanced through structural modification of its main skeleton. Currently, it has been reported to show significant inhibitory effects on disease models such as tumors, diabetes, cancer, tuberculosis, malaria, bacterial infections, and viral infections, demonstrating broad clinical transformation potential. In the field of materials science, the rigid conjugated characteristics of the skeleton endow it with excellent carrier mobility and environmental stability, making it an ideal candidate material for organic field-effect transistors (OFETs), flexible electronic devices, and wearable sensors. At the same time, its energy level structure and high fluorescence quantum yield not only enable the development of efficient organic light-emitting diodes (OLEDs) and organic solar cells (OPVs) but also promote innovative applications in biomedical fields such as photodetectors, metal ion fluorescent probes, and live cell imaging. In summary, pyrrolo[1,2-a]quinoxaline and its derivatives not only provide a molecular basis for drug design and materials engineering but also highlight the important theoretical value and practical application requirements for developing new substituted derivatives and precise synthesis strategies.

[0004] Since the thiol-yne addition reaction (i.e., hydrothiolation reaction) was first reported in 1930, this strategy has been widely used in the fields of organic synthesis and materials science due to its mild reaction conditions, simple operation, and high atom economy. However, compared with the mature application of terminal alkynes, the transformation of internal alkynes still faces significant challenges, which are mainly limited by the inherent properties of internal alkynes - the triple bond has relatively low reactivity, and there are challenges in the regioselectivity and stereochemical control during the addition process. Summary of the Invention

[0005] The present invention addresses the deficiencies in the above-mentioned background technology and provides a method for preparing thio-styryl pyrrolo[1,2-a]quinoxaline and its derivatives.

[0006] To achieve the above object, the present invention is realized through the following technical solutions:

[0007] A method for preparing thio-styryl pyrrolo[1,2-a]quinoxaline and its derivatives, comprising the following steps:

[0008] Perform a C-S coupling reaction using arylethynyl pyrrolo[1,2-a]quinoxaline and aryl mercaptan as the first reactants. After mixing the first reactants, an organic base, and a first solvent, stir at 80 - 120 °C for 24 - 48 h. After the reaction is completed, cool the reaction solution to room temperature, and then obtain thio-styryl pyrrolo[1,2-a]quinoxaline and its derivatives through separation and purification; or,

[0009] Perform a C-S coupling reaction using one of diaryl diselenide and aryl mercaptan, and arylethynyl pyrrolo[1,2-a]quinoxaline as the second reactants. Mix one of diaryl diselenide or aryl mercaptan with a second solvent, stir at room temperature for 5 - 15 min, then add arylethynyl pyrrolo[1,2-a]quinoxaline and an oxidant, and stir at room temperature for 15 - 30 min. After the reaction is completed, quench the reaction solution, and then obtain thio-styryl pyrrolo[1,2-a]quinoxaline and its derivatives through extraction, separation, and purification;

[0010] The reaction general formula of the C-S coupling reaction is as follows:

[0011]

[0012] Among them, R is selected from any one of hydrogen, benzene, 4-bromobenzene, 4-methoxybenzene, 4-fluorobenzene, and 4-chlorobenzene; the aryl mercaptan is selected from any one of p-toluenethiol, p-fluorobenzenethiol, p-chlorobenzenethiol, p-bromobenzenethiol, p-methoxybenzenethiol, p-hydroxybenzenethiol, p-nitrobenzenethiol, p-aminobenzenethiol, 2-methylbenzenethiol, 3-methylbenzenethiol, 2-fluorobenzenethiol, 3-fluorobenzenethiol, naphthalenethiol, thiophenol, and 2-methyl-3-furanthiol.

[0013] Under the preferred embodiment, the organic base is selected from one or more of 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), triethylamine, N,N-diisopropylethylamine (DIPEA), 4-dimethylaminopyridine (DMAP), 1,4-diazabicyclo[2.2.2]octane (DABCO), and imidazole; the oxidant is selected from one or more of ammonium persulfate, potassium persulfate, sodium persulfate, and potassium hydrogen persulfate.

[0014] Under the preferred embodiment, the first solvent and the second solvent are each independently selected from one or more of dichloromethane, dimethyl sulfoxide, N,N-dimethylformamide, acetonitrile, ethanol, and 1,4-dioxane.

[0015] Under the preferred embodiment, the molar ratio of aryl thiol, arylethynylpyrrolo[1,2-a]quinoxaline, and organic base is 1.5:1:0.8; the molar ratio of diaryl diselenide, arylethynylpyrrolo[1,2-a]quinoxaline, and oxidant is 2:1:5.

[0016] Under the preferred embodiment, a heating plate is used to heat the mixture of the first reactant, the organic base, and the first solvent.

[0017] Under the preferred embodiment, in the reaction involving the oxidant, the reaction solution is quenched with saturated sodium bicarbonate solution.

[0018] Under the preferred embodiment, the extraction is to repeatedly extract the organic phase of the quenched reaction solution with an extractant and combine the organic phases; the separation and purification is to remove the solvent under reduced pressure to obtain a crude product, and then rapidly chromatographically purify the crude product on silica gel to obtain (Z)-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline and its derivatives.

[0019] Under the preferred embodiment, the extractant is ethyl acetate.

[0020] Under the preferred embodiment, a mixed solution of petroleum ether and ethyl acetate is used as the eluent, and the crude product is rapidly chromatographically purified on silica gel, and the volume ratio of petroleum ether to ethyl acetate is (5-20):1.

[0021] The beneficial effects of the present invention are as follows:

[0022] The present invention selects the structurally complex 1-(phenylethynyl)pyrrolo[1,2-a]quinoxaline as the model substrate, breaks through the research limitations of the traditional functionalization of the C1 / C3 sites of pyrroloquinoxaline, and for the first time expands the modification site to the alkynyl α-H position. This strategy not only provides a new idea for the selective functionalization of alkynyl-containing heterocyclic compounds, but also opens up a new way for the design of new functional molecules and the development of high-performance polymers. Detailed Embodiments

[0023] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without making creative efforts shall fall within the protection scope of the present invention.

[0024] In the present invention, unless otherwise specified, the scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. The experimental methods in the embodiments are all conventional methods unless otherwise specified. For those conditions not specified in the embodiments, they are carried out according to the conventional conditions or the conditions recommended by the manufacturer. For the reagents or instruments whose manufacturers are not specified, they are all conventional products that can be obtained through commercial purchase.

[0025] The present invention uses arylethynylpyrrolo[1,2-a]quinoxaline and aryl mercaptan or diaryl diselenide as reactants to prepare thiostyryl pyrrolo[1,2-a]quinoxaline and its derivatives, namely (Z)-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline and its derivatives, including the following steps:

[0026] React arylethynylpyrrolo[1,2-a]quinoxaline, aryl mercaptan, organic base and solvent in a pressure-resistant tube. Stir the mixture in air at 80-120 °C for 24-48 hours. After the reaction is completed, cool to room temperature, and remove the solvent by rotary evaporation under reduced pressure. Purify the crude product by flash chromatography on silica gel (the time is generally controlled within 12 h) to obtain the final product (Z)-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline and its derivatives.

[0027] React arylethynylpyrrolo[1,2-a]quinoxaline, diphenyl diselenide 、 oxidant and solvent in a pressure-resistant tube. Stir the mixture at room temperature for half an hour. After the reaction is completed, cool to room temperature. Quench with saturated aqueous sodium bicarbonate solution, extract and separate with ethyl acetate, combine the organic phases, and remove the solvent by rotary evaporation under reduced pressure. Purify the crude product by flash chromatography on silica gel (the time is generally controlled within 12 h) to obtain the final product (E)-1-(2-phenyl-1,2-bis(phenylseleno)vinyl)pyrrolo[1,2-a]quinoxaline and its derivatives.

[0028] Among them, the arylthiol is benzenethiol or naphthol or other heterocyclic thiols with various substituents; specifically, the arylthiol is selected from p-toluenethiol, p-fluorobenzenethiol, p-chlorobenzenethiol, p-bromobenzenethiol, p-methoxybenzenethiol, p-hydroxybenzenethiol, p-nitrobenzenethiol, p-aminobenzenethiol, 2-methylbenzenethiol, 3-methylbenzenethiol, 2-fluorobenzenethiol, 3-fluorobenzenethiol, naphthalenethiol, thiophenol or 2-methyl-3-furanthiol.

[0029] The organic base can be but is not limited to 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), triethylamine, N,N-diisopropylethylamine (DIPEA), 4-dimethylaminopyridine (DMAP), 1,4-diazabicyclo[2.2.2]octane (DABCO), imidazole.

[0030] The solvent is selected from one or more of dichloromethane, dimethyl sulfoxide, N,N-dimethylformamide, acetonitrile, ethanol and 1,4-dioxane.

[0031] The oxidant is selected from one or more of ammonium persulfate, potassium persulfate, sodium persulfate and potassium peroxymonosulfate.

[0032] In some embodiments, generally based on the amount of arylethynylpyrrolo[1,2-a]quinoxaline, 0.2 mmol is generally added. When the amount of the oxidant is reduced to 1 equivalent, the yield significantly decreases. Therefore, the amount of the oxidant is preferably controlled above 1 equivalent.

[0033] The general formula of the C-S coupling reaction is as follows:

[0034]

[0035] In the formula, R is the substituent at the 4-position on pyrrolo[1,2-a]quinoxaline, and is selected from the following groups (one of them): hydrogen, benzene, 4-bromobenzene, 4-methoxybenzene, 4-fluorobenzene, 4-chlorobenzene.

[0036] The molar ratio of arylthiol to arylethynylpyrrolo[1,2-a]quinoxaline is 1.5:1.

[0037] The molar ratio of diaryl diselenide to arylethynylpyrrolo[1,2-a]quinoxaline is 2:1.

[0038] The molar ratio of the oxidant to arylethynylpyrrolo[1,2-a]quinoxaline is 5:1.

[0039] The molar ratio of the organic base to arylethynylpyrrolo[1,2-a]quinoxaline is 0.8:1.

[0040] The reactor is heated by a heating plate.

[0041] The reaction temperature is from rt to 120 °C, the time is from 0.5 to 48 h, preferably from 0.5 to 24 h; wherein, rt represents room temperature, generally about 25 °C.

[0042] Example 1: Synthesis of (Z)-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline

[0043] A preparation method of (Z)-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline, and its reaction formula is as follows:

[0044]

[0045] Specifically, it includes the following steps:

[0046] Add 1-phenylethynylpyrrolo[1,2-a]quinoxaline (53.7 mg, 0.2 mmol), p-toluenethiol (37.3 mg, 0.3 mmol), imidazole (10.9 mg, 0.8 equivalent) and acetonitrile (1 mL) into a 10 mL pressure-resistant tube. Stir the mixture at 120 °C for 48 hours. After the reaction is completed, cool it to room temperature, remove the solvent by rotary evaporation under reduced pressure, and purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) within 12 h to obtain the final product (Z)-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline 70.4 mg, with a yield of 93%, and Z / E = 5:1.

[0047] The nuclear magnetic resonance identification results of (Z)-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0048] 11H NMR (400 MHz, CDCl3) δ 8.75 (s, 1H), 8.62 (s, 0.2×1H), 8.25 (d, J = 9.5 Hz, 1 + 0.2×1H), 7.99 (d, J = 9.4 Hz, 1 + 0.2×1H), 7.75 (d, J = 7.3 Hz, 2H), 7.52 (d, J = 7.8 Hz, 0.2×2H), 7.45 (d, J = 7.0 Hz, 3 + 0.2×3H), 7.37 (m, 0.2×4H), 7.36 - 7.27 (m, 4H), 7.20 (d, J = 7.7 Hz, 0.2×2H), 7.07 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 4.2 Hz, 1H), 6.86 (d, J = 7.9 Hz, 2H), 6.65 (d, J = 6.5 Hz, 0.2×2H), 6.11 (d, J = 4.0 Hz, 0.2×1H), 2.33 (s, 0.2×3H), 2.15 (s, 3H);

[0049] 13 13C NMR (101 MHz, CDCl3, for Z) δ 145.51, 139.78, 138.30, 137.52, 136.28, 134.12, 131.02, 130.33, 129.93, 129.79, 129.51, 129.38, 128.50, 128.14, 127.51, 127.35, 125.15, 124.32, 117.21, 116.74, 107.71, 20.96.

[0050] HRMS (APCI): m / z calcd for C 26 H 20 N2S (M + H) + : 393.1420, found: 393.1413.

[0051] Example 2: Synthesis of (Z)-1-(2-((4-fluorophenyl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-((4-fluorophenyl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline

[0052] A preparation method of (Z)-1-(2-((4-fluorophenyl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-((4-fluorophenyl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline, and its reaction formula is as follows:

[0053]

[0054] Specifically, it includes the following steps:

[0055] Add 1-phenylethynylpyrrolo[1,2-a]quinoxaline (53.7 mg, 0.2 mmol), p-fluorothiophenol (38.5 mg, 0.3 mmol), imidazole (10.9 mg, 0.8 equiv.) and acetonitrile (1 mL) into a 10 mL pressure-resistant tube. Stir the mixture at 120 °C for 48 hours. After the reaction is completed, cool it to room temperature, remove the solvent by rotary evaporation under reduced pressure, and purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (Z)-1-(2-((4-fluorophenyl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-((4-fluorophenyl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline, 65.8 mg, with a yield of 83%, and Z / E = 10:1.

[0056] The NMR identification results of (Z)-1-(2-((4-fluorophenyl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-((4-fluorophenyl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0057] 1 H NMR(400MHz,CDCl3)δ8.69(s,1H),8.56(s,0.1×1H),8.23 - 8.11(m,1 + 0.1×1H),7.92(dd,J=7.1,2.4Hz,1 + 0.1×1H),7.62(d,J=6.9Hz,2H),7.47(dd,J=8.7,5.3Hz,0.1×2H),7.39(dd,J=6.6,2.9Hz,2H),7.35(s,1 + 0.1×1H),7.32 - 7.29(m,0.1×2H),7.25(dt,J=12.6,6.9Hz,3H),7.20(s,0.1×1H),7.18(s,1H),7.16 - 7.12(m,0.1×3H),7.08(dd,J=8.7,5.2Hz,2H),6.98(d,J=8.6Hz,0.2×1H),6.87(d,J=4.2Hz,1H),6.73(s,0.1×1H),6.69(t,J=8.7Hz,2H),6.57(d,J=4.2Hz,0.1×1H),6.05(d,J=4.2Hz,0.1×1H);

[0058] 1313C NMR (101 MHz, CDCl3, for Z) δ 145.65, 139.33, 136.45, 134.24, 134.09, 132.47, 131.91, 130.90, 130.09, 129.63, 128.85, 128.77, 128.54, 128.05, 127.55, 125.62, 125.37, 120.20, 117.26, 116.70, 107.76, 101.69;

[0059] 19 19F NMR (376 MHz, CDCl3) δ -100.01.

[0060] HRMS (APCI): m / z calcd for C 25 H 17 FN2S (M + H) + : 397.1169, found: 397.1161.

[0061] Example 3: Synthesis of (Z)-1-(2-Phenyl-2-(o-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-Phenyl-2-(o-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline

[0062] A preparation method of (Z)-1-(2-Phenyl-2-(o-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-Phenyl-2-(o-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline, and its reaction formula is as follows:

[0063]

[0064] Specifically, it includes the following steps:

[0065] Add 1-phenylethynylpyrrolo[1,2-a]quinoxaline (53.7 mg, 0.2 mmol), 2-methylbenzenethiol (37.3 mg, 0.3 mmol), imidazole (10.9 mg, 0.8 eq) and acetonitrile (1 mL) into a 10 mL pressure-resistant tube. Stir the mixture at 120 °C for 48 hours. After the reaction is completed, cool it to room temperature, remove the solvent by rotary evaporation under reduced pressure, and purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (Z)-1-(2-Phenyl-2-(o-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-Phenyl-2-(o-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline 70.7 mg, with a yield of 90%, and Z / E = 3:1.

[0066] The NMR identification results of (Z)-1-(2-phenyl-2-(o-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(o-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0067] 1 H NMR(400MHz,CDCl3)δ8.66(s,1H),8.52(s,0.3×1H),8.18(dd,J=6.4,3.1Hz,1H),8.02(d,J=7.8Hz,0.3×1H),7.93-7.87(m,1H),7.83(s,0.3×1H),7.63(d,J=7.3Hz,2H),7.56(s,0.3×1H),7.42(s,1H),7.40-7.35(m,2H),7.33(d,J=7.0Hz,1+0.3×1H),7.27-7.20(m,2+0.3×3H),7.20-7.16(m,3H),7.15(s,0.3×1H),7.03(d,J=7.6Hz,1H),6.91(d,J=7.3Hz,1H),6.87-6.81(m,2H),6.78(d,J=7.3Hz,1H),6.53(d,J=4.2Hz,0.3×1H),6.37(s,0.3×1H),6.00(d,J=4.2Hz,0.3×1H),2.54(s,0.3×3H),2.29(s,3H);

[0068] 13 C NMR(101MHz,CDCl3,for Z)δ145.61,139.82,137.79,137.67,137.63,135.93,133.89,131.17,130.27,130.16,129.95,129.45,129.26,128.65,128.59,128.00,127.70,127.50,126.53,126.29,125.31,124.86,117.19,116.78,107.84,20.64.

[0069] HRMS(APCI):m / z calcd for C 26 H 20 N2S(M+H) + :393.1420,found:393.1414.

[0070] Example 4: Synthesis of (Z)-1-(2-phenyl-2-(m-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(m-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline

[0071] A preparation method of (Z)-1-(2-phenyl-2-(m-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(m-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline, and its reaction formula is as follows:

[0072]

[0073] Specifically, it includes the following steps:

[0074] Add 1-aryl ethynyl pyrrolo[1,2-a]quinoxaline (53.7 mg, 0.2 mmol), m-toluenethiol (37.3 mh, 0.3 mmol), imidazole (10.9 mg, 0.8 equivalent) and acetonitrile (1 mL) into a 10 mL pressure-resistant tube. Stir the mixture at 120 °C for 48 hours. After the reaction is completed, cool it to room temperature, remove the solvent by rotary evaporation under reduced pressure, and purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (Z)-1-(2-phenyl-2-(m-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(m-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline 68.3 mg, with a yield of 87%, and Z / E = 3:1.

[0075] The nuclear magnetic resonance identification results of (Z)-1-(2-phenyl-2-(m-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(m-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0076] 11H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 8.56 (s, 0.3×1H), 8.24 - 8.08 (m, 1 + 0.3×1H), 7.98 - 7.83 (m, 1 + 0.3×1H), 7.70 (d, J = 7.2 Hz, 2H), 7.41 (s, 1H), 7.39 (s, 1H), 7.38 (d, J = 4.7 Hz, 1 + 0.3×2H), 7.35 (s, 0.3×3H), 7.29 (q, J = 6.8 Hz, 2H), 7.24 (s, 1H), 7.22 - 7.14 (m, 2 + 0.3×2H), 7.05 (d, J = 7.6 Hz, 0.3×1H), 6.94 (s, 1H), 6.89 (t, J = 7.1 Hz, 1 + 0.3×1H), 6.85 (d, J = 4.3 Hz, 1 + 0.3×2H), 6.71 (d, J = 7.2 Hz, 1H), 6.66 (s, 0.3×1H), 6.57 (d, J = 4.2 Hz, 0.3×1H), 6.06 (d, J = 4.2 Hz, 0.3×1H), 2.28 (s, 0.3×3H), 2.03 (s, 3H);

[0077] 13 13C NMR (101 MHz, CDCl3, for Z) δ 145.46, 139.93, 138.60, 134.59, 134.48, 130.89, 130.21, 129.82, 129.66, 129.50, 128.73, 128.64, 128.61, 128.53, 128.17, 127.53, 127.21, 126.72, 125.32, 124.67, 117.33, 116.79, 107.96, 21.25.

[0078] HRMS (APCI): m / z calcd for C 26 H 20 N2S (M + H) + : 393.1420, found: 393.1417.

[0079] Example 5: Synthesis of (Z)-1-(2-(naphthalen-2-ylthio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(naphthalen-2-ylthio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline

[0080] A preparation method of (Z)-1-(2-(naphthalen-2-ylthio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(naphthalen-2-ylthio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline, and the reaction formula is as follows:

[0081]

[0082] Specifically, it includes the following steps:

[0083] Add 1-phenylethynylpyrrolo[1,2-a]quinoxaline (53.7 mg, 0.2 mmol), 2-naphthalenethiol (48.1 mg, 0.3 mmol), imidazole (10.9 mg, 0.8 equivalent) and acetonitrile (1 mL) into a 10 mL pressure-resistant tube. Stir the mixture at 120 °C for 48 hours. After the reaction is completed, cool it to room temperature, remove the solvent by rotary evaporation under reduced pressure, and purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (Z)-1-(2-(naphthalen-2-ylthio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(naphthalen-2-ylthio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline 70.7 mg, with a yield of 90%, and Z / E = 3:1.

[0084] The nuclear magnetic resonance identification results of (Z)-1-(2-(naphthalen-2-ylthio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(naphthalen-2-ylthio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0085] 1 H NMR (400 MHz, CDCl3) δ 8.71 (s, 1H), 8.62 (s, 1H), 8.28 (d, J = 9.2 Hz, 1H), 8.23 (d, J = 8.3 Hz, 1H), 8.11 (s, 1H), 7.99 (t, J = 7.3 Hz, 2H), 7.82 (dd, J = 7.7, 4.8 Hz, 5H), 7.64 (d, J = 9.8 Hz, 3H), 7.56 (d, J = 6.9 Hz, 2H), 7.54 - 7.43 (m, 7H), 7.39 - 7.31 (m, 6H), 7.31 - 7.27 (m, 2H), 7.25 - 7.21 (m, 3H), 7.18 - 7.13 (m, 1H), 6.92 (d, J = 4.2 Hz, 1H), 6.84 (s, 1H), 6.69 (d, J = 4.2 Hz, 1H), 6.17 (d, J = 4.2 Hz, 1H);

[0086] 1313C NMR (101 MHz, DMSO, for Z) δ 156.70, 145.70, 139.00, 138.90, 137.09, 132.61, 129.48, 129.08, 128.82, 128.56, 128.41, 128.34, 128.26, 128.13, 127.74, 126.96, 125.23, 123.19, 121.67, 117.33, 116.59, 115.96, 107.69, 40.15, 39.94, 39.73, 39.52, 39.31, 39.10, 38.89。

[0087] HRMS (APCI): m / z calcd for C 29 H 20 N2S (M + H) + : 429.1420, found: 429.1416.

[0088] Example 6: Synthesis of (Z)-1-(2-phenyl-2-(thiophen-2-ylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(thiophen-2-ylthio)vinyl)pyrrolo[1,2-a]quinoxaline

[0089] A preparation method of (Z)-1-(2-phenyl-2-(thiophen-2-ylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(thiophen-2-ylthio)vinyl)pyrrolo[1,2-a]quinoxaline, and its reaction formula is as follows:

[0090]

[0091] Specifically, it includes the following steps:

[0092] Add 1-phenylethynylpyrrolo[1,2-a]quinoxaline (53.7 mg, 0.2 mmol), thiophene-2-thiol (34.8 mg, 0.3 mmol), imidazole (10.9 mg, 0.8 equivalent) and acetonitrile (1 mL) into a 10 mL pressure-resistant tube. Stir the mixture at 120 °C for 48 hours. After the reaction is completed, cool it to room temperature, remove the solvent by rotary evaporation under reduced pressure, and purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (Z)-1-(2-phenyl-2-(thiophen-2-ylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(thiophen-2-ylthio)vinyl)pyrrolo[1,2-a]quinoxaline 70.0 mg, with a yield of 91%, and Z / E = 1:1.

[0093] Nuclear magnetic resonance identification results of (Z)-1-(2-phenyl-2-(thiophen-2-ylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-phenyl-2-(thiophen-2-ylthio)vinyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0094] 1 H NMR(400MHz,CDCl3)δ8.79(s,1H),8.63(s,0.7×1H),8.30 - 8.19(m,1 + 0.7×1H),8.06 - 7.95(m,1 + 0.7×1H),7.67(d,J=7.3Hz,2H),7.53(d,J=5.4Hz,0.7×1H),7.47(dd,J=8.3,4.9Hz,2 + 0.7×2H),7.41 - 7.36(m,2 + 0.7×2H),7.36 - 7.31(m,1 + 0.7×2H),7.29(d,J=5.4Hz,2H),7.25(d,J=6.0Hz,0.7×2H),7.10(dd,J=12.4,5.1Hz,1 + 0.7×1H),7.01(d,J=4.1Hz,1H),6.93(d,J=3.5Hz,1H),6.77 - 6.70(m,1H),6.67(d,J=4.1Hz,0.7×1H),6.62(s,0.7×1H),6.12(d,J=4.2Hz,0.7×1H);

[0095] 13 C NMR(101MHz,CDCl3,for Z)δ145.72,136.95,133.70,132.24,129.94,129.50,129.35,128.61,128.50,128.42,127.44,127.07,125.23,122.73,117.62,116.70,116.32,107.83,107.64.

[0096] HRMS(APCI):m / z calcd for C 23 H 16 N2S2(M + H) + :385.0828,found:385.0822.

[0097] Example 7:Synthesis of (Z)-1-(2-((5-methylfuran-2-yl)thio)-2-phenylvinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-((5-methylfuran-2-yl)thio)-2-phenylvinyl)pyrrolo[1,2-a]quinoxaline

[0098] A preparation method of (Z)-1-(2-((5-methylfuran-2-yl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-((5-methylfuran-2-yl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline, and the reaction formula is as follows:

[0099]

[0100] Specifically, it includes the following steps:

[0101] Add 1-phenylethynylpyrrolo[1,2-a]quinoxaline (53.7 mg, 0.2 mmol), 5-methylfuran-2-thiol (34.2 mg, 0.3 mmol), imidazole (10.9 mg, 0.8 eq), and acetonitrile (1 mL) into a 10 mL pressure-resistant tube. Stir the mixture at 120 °C for 48 hours. After the reaction is completed, cool it to room temperature, remove the solvent by rotary evaporation under reduced pressure, and purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (Z)-1-(2-((5-methylfuran-2-yl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-((5-methylfuran-2-yl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline 60.4 mg, with a yield of 79%, and Z / E = 2:1.

[0102] The nuclear magnetic resonance identification results of (Z)-1-(2-((5-methylfuran-2-yl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-((5-methylfuran-2-yl)thio)-2-phenylethenyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0103] 11H NMR (400 MHz, CDCl3) δ 8.70 (s, 1H), 8.55 (s, 0.5×1H), 8.29 - 8.21 (m, 1H), 8.17 (dd, J = 6.2, 3.5 Hz, 0.5×1H), 7.94 - 7.86 (m, 1 + 0.5×1H), 7.50 (d, J = 6.7 Hz, 2H), 7.42 - 7.35 (m, 2 + 0.5×2H), 7.33 - 7.27 (m, 2 + 0.5×2H), 7.24 (d, J = 6.9 Hz, 0.5×2H), 7.20 (dd, J = 7.4, 3.1 Hz, 2 + 0.5×2H), 7.09 (s, 1H), 6.91 (d, J = 4.2 Hz, 1H), 6.88 (d, J = 1.9 Hz, 1H), 6.56 (d, J = 4.2 Hz, 0.5×1H), 6.51 (s, 0.5×1H), 6.43 (d, J = 1.8 Hz, 0.5×1H), 6.01 (d, J = 4.0 Hz, 0.5×1H), 5.93 (d, J = 1.8 Hz, 1H), 2.40 (s, 0.5×3H), 2.11 (s, 3H);

[0104] 13 13C NMR (101 MHz, CDCl3, for Z) δ 154.73, 145.70, 141.64, 140.48, 129.92, 129.25, 128.60, 128.50, 128.37, 128.32, 127.38, 125.26, 120.94, 117.67, 116.71, 116.59, 115.41, 114.62, 107.75, 12.06.

[0105] HRMS (APCI): m / z calcd for C 24 H 18 N2OS (M + H) + : 383.1213, found: 383.1207.

[0106] Example 8: Synthesis of (Z)-4-phenyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-4-phenyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline

[0107] A preparation method of (Z)-4-phenyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-4-phenyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline, and its reaction formula is as follows:

[0108]

[0109] Specifically, the following steps are included:

[0110] Add 4-phenyl-1-phenylethynylpyrrolo[1,2-a]quinoxaline (53.7 mg, 0.2 mmol), p-toluenethiol (37.3 mg, 0.3 mmol), imidazole (10.9 mg, 0.8 equiv), and acetonitrile (1 mL) into a 10 mL pressure-resistant tube. Stir the mixture at 120 °C for 48 hours. After the reaction is completed, cool it to room temperature, and remove the solvent by rotary evaporation under reduced pressure. Purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (Z)-4-phenyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-4-phenyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline, 66.5 mg, with a yield of 71%, and Z / E = 5:1.

[0111] The NMR identification results of (Z)-4-phenyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-4-phenyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0112] 11H NMR (400 MHz, CDCl3, for method one) δ 8.23 - 8.14 (m, 1 + 0.2×1H), 7.97 (dd, J = 6.1, 3.5 Hz, 1 + 0.2×1H), 7.87 (dd, J = 7.4, 1.9 Hz, 2H), 7.77 (dd, J = 6.6, 2.9 Hz, 0.2×2H), 7.67 (d, J = 7.6 Hz, 2H), 7.47 (d, J = 3.7 Hz, 0.2×2H), 7.44 (d, J = 6.2 Hz, 2 + 0.2×2H), 7.42 (d, J = 4.0 Hz, 0.2×3H), 7.37 (d, J = 5.9 Hz, 2 + 0.2×1H), 7.35 (dd, J = 5.1, 2.1 Hz, 2H), 7.25 (t, J = 7.3 Hz, 2H), 7.19 (dd, J = 14.0, 5.7 Hz, 2H), 7.16 - 7.12 (m, 0.2×4H), 7.09 (d, J = 8.0 Hz, 0.2×2H), 6.98 (d, J = 8.1 Hz, 2H), 6.89 (d, J = 4.3 Hz, 1H), 6.75 (d, J = 8.0 Hz, 2H), 6.62 (s, 0.2×1H), 6.60 (d, J = 4.3 Hz, 0.2×1H), 6.02 (d, J = 4.3 Hz, 0.2×1H), 2.23 (s, 0.2×3H), 2.05 (s, 3H);

[0113] 13 13C NMR (101 MHz, CDCl3, for Z) δ 154.39, 139.83, 136.28, 134.07, 131.05, 130.32, 129.97, 129.76, 129.48, 128.92, 128.73, 128.67, 128.62, 128.50, 128.42, 128.15, 126.99, 126.53, 125.24, 124.52, 117.24, 116.61, 109.07, 20.97.

[0114] HRMS (APCI): m / z calcd for C 32 H 24 N2S (M + H) + : 469.1733, found: 469.1729.

[0115] Example 9: Synthesis of (Z)-1-(2-(p-tolyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(p-tolyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline

[0116] A preparation method of (Z)-1-(2-(p-tolyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(p-tolyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline, and its reaction formula is as follows:

[0117] Specifically, it includes the following steps:

[0118]

[0119] Add 1-(p-tolylethynyl)pyrrolo[1,2-a]quinoxaline (56.5 mg, 0.2 mmol), p-toluenethiol (37.3 mg, 0.3 mmol), imidazole (10.9 mg, 0.8 equivalent) and acetonitrile (1 mL) into a 10 mL pressure-resistant tube. Stir the mixture at 120 °C for 48 hours. After the reaction is completed, cool it to room temperature, remove the solvent under reduced pressure, and purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (Z)-1-(2-(p-tolyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(p-tolyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline 57.7 mg, with a yield of 71% and Z / E = 3:1.

[0120] The nuclear magnetic resonance identification results of (Z)-1-(2-(p-tolyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(p-tolyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0121] 11H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H), 8.53 (s, 0.3×3H), 8.14 (dd, J = 6.2, 3.5 Hz, 1 + 0.3×3H), 7.88 (dd, J = 6.3, 3.3 Hz, 1 + 0.3×3H), 7.57 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.1 Hz, 0.3×2H), 7.39 - 7.29 (m, 3 + 0.3×2H), 7.22 (d, J = 8.0 Hz, 0.3×2H), 7.16 (d, J = 4.0 Hz, 1H), 7.10 (d, J = 7.9 Hz, 0.3×2H), 7.07 (d, J = 8.0 Hz, 2H), 6.97 (t, J = 9.0 Hz, 2 + 0.3×2H), 6.82 (d, J = 4.2 Hz, 1H), 6.77 (d, J = 8.0 Hz, 2H), 6.55 (d, J = 4.2 Hz, 0.3×3H), 6.52 (s, 0.3×3H), 6.05 (d, J = 4.2 Hz, 0.3×1H), 2.26 (s, 3H), 2.24 (s, 0.3×3H), 2.21 (s, 0.3×3H), 2.06 (s, 3H);

[0122] 13 13C NMR (101 MHz, CDCl3, for Z) δ 197.26, 145.57, 138.69, 138.23, 136.99, 136.19, 134.13, 131.40, 130.40, 129.83, 129.74, 129.68, 129.58, 129.34, 129.29, 129.24, 128.05, 127.38, 125.20, 123.93, 117.14, 116.85, 107.78, 21.34, 21.03.

[0123] HRMS (APCI): m / z calcd for C 27 H 22 N2S (M + H) + : 407.1576, found: 407.1570.

[0124] Example 10: Synthesis of (Z)-1-(2-(4-chlorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(4-chlorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline

[0125] A preparation method of (Z)-1-(2-(4-chlorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(4-chlorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline, and the reaction formula is as follows:

[0126]

[0127] Specifically, it includes the following steps:

[0128] Add 1-(p-chlorophenylethynyl)pyrrolo[1,2-a]quinoxaline (60.6 mg, 0.2 mmol), p-toluenethiol (37.3 mg, 0.3 mmol), imidazole (10.9 mg, 0.8 equivalent) and acetonitrile (1 mL) into a 10 mL pressure-resistant tube. Stir the mixture at 120 °C for 48 hours. After the reaction is completed, cool it to room temperature, remove the solvent by rotary evaporation under reduced pressure, and purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (Z)-1-(2-(4-chlorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(4-chlorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline 83.7 mg, with a yield of 98%, and Z / E = 1:1.

[0129] The nuclear magnetic resonance identification results of (Z)-1-(2-(4-chlorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(4-chlorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0130] 1 H NMR(400MHz,CDCl3)δ8.68(s,1H),8.57(s,1H),8.18 - 8.03(m,2H),7.97 - 7.82(m,2H),7.59(d,J = 8.5Hz,2H),7.42 - 7.36(m,6H),7.34(s,1H),7.27(d,J = 8.5Hz,2H),7.24 - 7.21(m,3H),7.18(s,1H),7.11(dd,J = 8.1,6.2Hz,4H),6.99(d,J = 8.1Hz,2H),6.87(d,J = 4.2Hz,1H),6.81(d,J = 8.0Hz,2H),6.68(s,1H),6.59(d,J = 4.2Hz,1H),6.05(d,J = 4.2Hz,1H),2.25(s,3H),2.11(s,3H);

[0131] 13 13C NMR (101 MHz, CDCl3, for Z) δ 145.58, 139.23, 138.42, 135.96, 134.41, 133.94, 130.90, 130.48, 130.07, 129.79, 129.41, 128.83, 127.55, 127.22, 125.39, 124.76, 118.30, 117.41, 116.77, 116.62, 107.96, 21.09.

[0132] HRMS (APCI): m / z calcd for C 26 H 19 ClN2S (M + H) + : 427.1030, found: 427.1025.

[0133] Example 11: Synthesis of (Z)-3-(2-Phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-3-(2-Phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline

[0134] A preparation method of (Z)-3-(2-Phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-3-(2-Phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline, and the reaction formula is as follows:

[0135]

[0136] Specifically, it includes the following steps:

[0137] Add 3-(phenylethynyl)pyrrolo[1,2-a]quinoxaline (53.7 mg, 0.2 mmol), p-toluenethiol (37.3 mg, 0.3 mmol), imidazole (10.9 mg, 0.8 equivalent) and acetonitrile (1 mL) into a 10 mL pressure-resistant tube. Stir the mixture at 120 °C for 48 hours. After the reaction is completed, cool it to room temperature, and remove the solvent by rotary evaporation under reduced pressure. Purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (Z)-3-(2-Phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-3-(2-Phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline 69 mg, with a yield of 88%, and Z / E = 10:1.

[0138] Nuclear magnetic resonance identification results of (Z)-3-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-3-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0139] 1 H NMR(400MHz,CDCl3)δ8.91(s,1H),8.62(s,0.1×1H),7.88(d,J=7.8Hz,1H),7.82(d,J=7.4Hz,0.1×2H),7.77(d,J=3.2Hz,2H),7.71(d,J=8.1Hz,1H),7.63-7.57(m,2H),7.55(s,0.1×1H),7.46-7.40(m,2+0.1×2H),7.36(t,J=8.1Hz,1H),7.31(s,0.1×3H),7.20(t,J=7.4Hz,2+0.1×3H),7.16-7.09(m,1+0.1×4H),7.04(d,J=8.2Hz,2H),7.00(d,J=7.9Hz,0.1×3H),6.84(d,J=8.0Hz,2H),5.84(d,J=2.9Hz,0.1×1H),2.21(s,0.1×3H),2.10(s,3H);

[0140] 13 C NMR(101MHz,CDCl3,for Z)δ143.57,141.49,135.83,133.24,133.07,131.77,130.14,128.97,128.41,128.38,127.94,127.84,125.70,124.87,114.84,114.40,113.89,21.07.

[0141] HRMS(APCI):m / z calcd for C 26 H 20 N2S(M+H) + :393.1420,found:393.1412.

[0142] Example 12: Synthesis of (Z)-3-(2-(p-tolyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-3-(2-(4-fluorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline

[0143] A preparation method of (Z)-3-(2-(p-tolyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-3-(2-(4-fluorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline, and the reaction formula is as follows:

[0144]

[0145] Specifically, it includes the following steps:

[0146] Add 3-(p-fluoroethynyl)pyrrolo[1,2-a]quinoxaline (57.3 mg, 0.2 mmol), p-toluenethiol (37.3 mg, 0.3 mmol), imidazole (10.9 mg, 0.8 equivalent), and acetonitrile (1 mL) into a 10 mL pressure-resistant tube. Stir the mixture at 120 °C for 48 hours. After the reaction is completed, cool it to room temperature, and remove the solvent by rotary evaporation under reduced pressure. Purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (Z)-1-(2-(4-chlorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(4-chlorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline 45.2 mg, with a yield of 55%, and Z / E = 4:1.

[0147] The nuclear magnetic resonance identification results of (Z)-1-(2-(4-chlorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-1-(2-(4-chlorophenyl)-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0148] 11H NMR (400 MHz, CDCl3) δ 9.00 (s, 1H), 8.75 (s, 0.25×1H), 7.99 (d, J = 7.9 Hz, 1H), 7.93 (d, J = 7.9 Hz, 0.25×1H), 7.89 (d, J = 2.9 Hz, 1H), 7.86 (d, J = 2.9 Hz, 1H), 7.82 (d, J = 7.7 Hz, 1H), 7.69 (d, J = 7.7 Hz, 0.25×1H), 7.64 (dd, J = 8.6, 5.5 Hz, 2H), 7.57 (d, J = 3.0 Hz, 0.25×1H), 7.53 (d, J = 7.1 Hz, 1H), 7.48 (d, J = 8.3 Hz, 1H), 7.45 (s, 1H), 7.42 - 7.37 (m, 0.25×2H), 7.34 (d, J = 8.1 Hz, 0.25×2H), 7.13 (d, J = 8.1 Hz, 2H), 7.10 (d, J = 8.1 Hz, 0.25×2H), 7.01 (d, J = 9.0 Hz, 1H), 6.96 (dd, J = 8.4, 3.5 Hz, 3 + 0.25×2H), 5.98 (d, J = 2.9 Hz, 0.25×1H), 2.32 (s, 0.25×3H), 2.22 (s, 3H).;

[0149] 13 13C NMR (101 MHz, CDCl3, for Z) δ 143.48, 136.13, 133.12, 132.32, 131.36, 130.13, 130.02, 129.79, 129.62, 129.54, 129.28, 128.42, 125.75, 124.42, 119.02, 115.41, 115.19, 114.85, 114.32, 113.89, 21.09;

[0150] 19 19F NMR (376 MHz, CDCl3, for 3zc) δ -114.27.

[0151] HRMS (APCI): m / z calcd for C 26 H 19 FN2S (M + H) + : 411.1326, found: 411.1320.

[0152] Example 13: Synthesis of (E)-1-(2-Phenyl-1,2-bis(phenylseleno)vinyl)pyrrolo[1,2-a]quinoxaline / (Z)-1-(2-Phenyl-1,2-bis(phenylseleno)vinyl)pyrrolo[1,2-a]quinoxaline

[0153] A preparation method of (E)-1-(2-phenyl-1,2-bis(phenylseleno)vinyl)pyrrolo[1,2-a]quinoxaline / (Z)-1-(2-phenyl-1,2-bis(phenylseleno)vinyl)pyrrolo[1,2-a]quinoxaline, and the reaction formula is as follows:

[0154]

[0155] Specifically, it includes the following steps:

[0156] Add diphenyl diselenide (124.9 mg, 0.4 mmol), ammonium persulfate (222.8 mg, 5 equivalents) and acetonitrile (0.5 mL) into a 10 mL pressure-resistant tube, stir the mixture at room temperature for 15 minutes, and then add 1-phenylethynylpyrrolo[1,2-a]quinoxaline (53.7 mg, 0.2 mmol) and acetonitrile (0.5 mL) into the tube. The reaction continues at room temperature for 30 minutes. After the reaction is completed, add saturated aqueous NaHCO3 solution (10 mL) to the reaction solution, and then extract with ethyl acetate (3×10 mL). Dry the organic layer with anhydrous Na2SO4, remove the solvent by rotary evaporation under reduced pressure, and purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (E)-1-(2-phenyl-1,2-bis(phenylseleno)vinyl)pyrrolo[1,2-a]quinoxaline / (Z)-1-(2-phenyl-1,2-bis(phenylseleno)vinyl)pyrrolo[1,2-a]quinoxaline 81.3 mg, with a yield of 70%, and Z / E = 10:1.

[0157] The nuclear magnetic resonance identification results of (E)-1-(2-phenyl-1,2-bis(phenylseleno)vinyl)pyrrolo[1,2-a]quinoxaline / (Z)-1-(2-phenyl-1,2-bis(phenylseleno)vinyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0158] 11H NMR (400 MHz, Chloroform-d) δ 8.67 (d, J = 8.4 Hz, 1H), 8.47 (d, J = 7.6 Hz, 0.1×1H), 8.47 (s, 1H), 8.27 (s, 0.1×1H), 7.84 (d, J = 8.2 Hz, 1H), 7.79 (dd, J = 8.0, 1.6 Hz, 0.1×1H), 7.55 - 7.50 (m, 1H), 7.49 - 7.45 (m, 0.1×1H), 7.42 (t, J = 7.0 Hz, 1H), 7.33 (d, J = 7.0 Hz, 0.1×1H), 7.24 (t, J = 7.4 Hz, 1 + 0.1×2H), 7.16 (d, J = 7.6 Hz, 2H), 7.14 - 7.08 (m, 2H), 7.07 - 7.01 (m, 1 + 0.1×1H), 6.96 (t, J = 7.4 Hz, 0.1×4H), 6.91 (dd, J = 7.6, 1.9 Hz, 0.1×2H), 6.89 - 6.80 (m, 3 + 0.1×2H), 6.77 (d, J = 6.7 Hz, 2 + 0.1×4H), 6.66 - 6.59 (m, 4H), 6.56 (d, J = 7.8 Hz, 0.1×1H), 6.34 (d, J = 4.1 Hz, 0.1×1H), 6.21 (d, J = 4.1 Hz, 0.1×1H);

[0159] 13 13C NMR (101 MHz, CDCl3, for Z) δ 145.18, 139.36, 136.48, 135.69, 134.71, 129.54, 129.10, 128.97, 128.55, 128.53, 128.37, 128.31, 127.94, 127.82, 127.37, 126.90, 126.66, 126.06, 125.28, 118.12, 117.20, 107.02.

[0160] HRMS (APCI): m / z calcd for C 31 H 22 N2Se2 (M + H) + : 583.0186, found: 583.0184.

[0161] Example 14: Synthesis of (Z)-7-methyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-7-methyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline

[0162] Preparation method of (Z)-7-methyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-7-methyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline, and reaction formula is as follows:

[0163]

[0164] Specifically, it includes the following steps:

[0165] Add p-toluenethiol (99.3 mg, 0.8 mmol), ammonium persulfate (222.8 mg, 5 equivalents) and dichloromethane (0.5 mL) into a 10 mL pressure-resistant tube, stir the mixture at room temperature for 15 minutes, and then add 7-methyl-1-(phenylethynyl)pyrrolo[1,2-a]quinoxaline (56.5 mg, 0.2 mmol) and dichloromethane (0.5 mL) into the tube. The reaction continues at room temperature for 30 minutes. After the reaction is completed, add saturated aqueous NaHCO3 solution (10 mL) to the reaction solution, and then extract with ethyl acetate (3×10 mL). Dry the organic layer with anhydrous Na2SO4, remove the solvent by rotary evaporation under reduced pressure, and purify the crude product by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to obtain the final product (Z)-7-methyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-7-methyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline 62.6 mg, with a yield of 77% and Z / E = 2:1.

[0166] Nuclear magnetic resonance identification results of (Z)-7-methyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline / (E)-7-methyl-1-(2-phenyl-2-(p-tolylthio)vinyl)pyrrolo[1,2-a]quinoxaline are as follows:

[0167] 11H NMR (400 MHz, CDCl3) δ 8.70 (s, 1H), 8.57 (s, 0.5×1H), 8.09 (dd, J = 10.6, 8.6 Hz, 1 + 0.5×1H), 7.74 (s, 1H), 7.71 (dt, J = 5.9, 1.3 Hz, 2 + 0.5×1H), 7.48 (d, J = 8.1 Hz, 0.5×2H), 7.42 (s, 1H), 7.40 - 7.35 (m, 1H), 7.33 (d, J = 1.5 Hz, 0.5×1H), 7.31 (d, J = 1.6 Hz, 1H), 7.30 (d, J = 1.3 Hz, 0.5×1H), 7.28 (t, J = 1.4 Hz, 0.5×1H), 7.26 (s, 1H), 7.25 - 7.23 (m, 2H), 7.22 - 7.19 (m, 0.5×3H), 7.16 (d, J = 7.9 Hz, 0.5×2H), 7.05 (d, J = 8.2 Hz, 2H), 6.87 (d, J = 4.2 Hz, 1H), 6.84 (d, J = 8.0 Hz, 2H), 6.66 (s, 0.5×1H), 6.57 (d, J = 4.2 Hz, 0.5×1H), 6.05 (d, J = 4.8 Hz, 0.5×1H), 2.47 (d, J = 7.1 Hz, 3 + 0.5×3H), 2.30 (s, 0.5×3H), 2.14 (s, 3H);

[0168] 13 13C NMR (101 MHz, CDCl3, for Z) δ 145.48, 139.86, 136.19, 134.99, 133.99, 131.12, 130.30, 129.80, 129.51, 129.40, 128.48, 128.41, 128.39, 128.09, 124.56, 116.95, 116.47, 116.30, 107.43, 21.01.

[0169] HRMS (APCI): m / z calcd for C 27 H 22 N2S (M + H) + : 407.1576, found: 407.1570.

[0170] As described above, it is only the preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution and inventive concept of the present invention, makes equivalent substitutions or changes, and all should be covered within the protection scope of the present invention.

Claims

1. A method for preparing thiostyrylpyrrolo[1,2-a]quinoxaline and its derivatives, characterized in that: The steps include: Using aromatic ethynyl pyrrolo[1,2-a]quinoxaline and aromatic thiophenol as the first reactant to carry out CS coupling reaction, the first reactant, the organic base and the first solvent are mixed, and stirred at 80 to 120° C. for 24 to 48 hours. After the reaction is completed, the reaction solution is cooled to room temperature, and then separated and purified to obtain thiostyryl pyrrolo[1,2-a]quinoxaline and its derivatives; or, A CS coupling reaction is carried out using one of diaryl diselenide and aromatic thiophenol and arylethynyl pyrrolo[1,2-a]quinoxaline as the second reactant, wherein the diaryl diselenide or one of aromatic thiophenol is mixed with a second solvent, stirred at room temperature for 5 to 15 minutes, and then arylethynyl pyrrolo[1,2-a]quinoxaline and an oxidant are added, stirred at room temperature for 15 to 30 minutes, and after the reaction is completed, the reaction solution is quenched, and then extracted, separated and purified to obtain thiostyryl pyrrolo[1,2-a]quinoxaline and its derivatives; The general reaction formula of the CS coupling reaction is as follows: Wherein, R is selected from any one of hydrogen, benzene, 4-bromobenzene, 4-methoxybenzene, 4-fluorobenzene and 4-chlorobenzene; the aromatic thiophenol is selected from any one of p-toluene thiophenol, p-fluorothiophenol, p-chlorothiophenol, p-bromothiophenol, p-methoxythiophenol, p-hydroxythiophenol, p-nitrothiophenol, p-aminothiophenol, 2-methylthiophenol, 3-methylthiophenol, 2-fluorothiophenol, 3-fluorothiophenol, naphthiophenol, thiophene alcohol and 2-methyl-3-furanthiol.

2. The method for preparing thiostyrylpyrrolo[1,2-a]quinoxaline and its derivatives according to claim 1, characterized in that: The organic base is selected from one or more of 1,8-diazacyclo[5,4,0]undecene-7 (DBU), triethylamine, N,N-diisopropylethylamine (DIPEA), 4-dimethylaminopyridine (DMAP), 1,4-diazidebicyclo[2.2.2]octane (DABCO) and imidazole; the oxidant is selected from one or more of ammonium persulfate, potassium persulfate, sodium persulfate and potassium hydrogen persulfate.

3. The method for preparing thiostyrylpyrrolo[1,2-a]quinoxaline and its derivatives according to claim 1, characterized in that: The first solvent and the second solvent are each independently selected from one or more of dichloromethane, dimethyl sulfoxide, N,N-dimethylformamide, acetonitrile, ethanol and 1,4-dioxane.

4. The method for preparing thiostyrylpyrrolo[1,2-a]quinoxaline and its derivatives according to claim 1, characterized in that: The molar ratio of aromatic thiophenol, aromatic ethynyl pyrrolo[1,2-a]quinoxaline and organic base is 1.5:1:0.8; the molar ratio of diaryl diselenide, aromatic ethynyl pyrrolo[1,2-a]quinoxaline and oxidant is 2:1:

5.

5. The method for preparing thiostyrylpyrrolo[1,2-a]quinoxaline and its derivatives according to claim 1, characterized in that: A heating plate is used to heat a mixture of the first reactant, the organic base and the first solvent.

6. The method for preparing thiostyrylpyrrolo[1,2-a]quinoxaline and its derivatives according to claim 1, characterized in that: In the reaction involving an oxidant, the reaction solution is quenched with a saturated sodium bicarbonate solution.

7. The method for preparing thiostyrylpyrrolo[1,2-a]quinoxaline and its derivatives according to claim 1, characterized in that: The separation and purification comprises removing the solvent by rotary evaporation under reduced pressure to obtain a crude product, and then purifying the crude product by rapid chromatography on silica gel to obtain (Z)-1-(2-phenyl-2-(p-toluenethio)vinyl)pyrrolo[1,2-a]quinoxaline and its derivatives.

8. The method for preparing thiostyrylpyrrolo[1,2-a]quinoxaline and its derivatives according to claim 7, characterized in that: The crude product was purified by flash chromatography on silica gel using a mixed solution of petroleum ether and ethyl acetate as eluent, wherein the volume ratio of petroleum ether to ethyl acetate was (5-20):1.

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