Method for catalytically synthesizing 1-bromo-2-styrene derivative through metal bromide

Abstract

The invention discloses a method for catalytically synthesizing a 1-bromo-2-styrene derivative through a metal bromide, which comprises the following steps: mixing a styryl sulfoxide compound serving as a substrate and the metal bromide serving as a bromine source, dissolving in a solvent, and directly reacting at a certain temperature to efficiently prepare a bromo-olefin derivative. Compared with the conventional synthesis method, the method provided by the invention has the advantages that the reaction only needs one step, peroxide, strong alkali, transition metal or ligand and the like are not required to be used as a catalyst or a bromine source, and the operation is simpler and safer. The method has good substrate applicability and can be compatible with mono-substituted and multi-substituted phenyl alkenyl sulfoxide compounds containing electron withdrawing or electron donating groups. Particularly, the strategy for synthesizing bromo-olefin by using metal bromides such as CuBr and the like as the catalyst is not reported before, and the highest product separation yield can reach 92% under optimized conditions.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis and research technology of highly active biopharmaceutical intermediate synthesis, specifically a method for synthesizing 1-bromo-2-styrene derivatives by catalysis of metal bromides. Background Technology

[0002] Halogenated alkenes, as a key intermediate in organic synthesis, have gained wide application due to their high reactivity and transformation flexibility. For example, 1-bromo-2-styrene and its derivatives have attracted continuous attention from researchers in recent years due to their unique reactivity and diverse functional potential. These compounds play important roles in multiple fields such as drug synthesis, agrochemicals, functional materials, and liquid crystal molecule construction. In the field of medicinal chemistry, 1-bromo-2-styrene derivatives can be structurally modified to introduce different pharmacophores (such as amino, hydroxyl, and halogen groups), thereby optimizing their bioactivity and selectivity, exhibiting potential pharmacological activities such as inhibiting tumor cell proliferation and regulating inflammatory responses, providing valuable candidate scaffolds for new drug development. In materials science, 1-bromo-2-styrene can participate in polymerization reactions as a functional monomer, or be used to prepare functional materials such as polymers with stimuli-responsive properties, ion exchange resins, and polymer catalyst supports through subsequent functionalization. In summary, 1-bromo-2-styrene and its derivatives, with their structural tunability and reactivity diversity, have become an important bridge connecting basic organic synthesis and cutting-edge applied research, and have broad development prospects.

[0003] In recent years, the synthesis methods for brominated alkenes have developed rapidly and have attracted continuous attention from chemists both domestically and internationally, with related research reports increasing year by year. Although the reported synthetic routes have shown a certain degree of broad substrate applicability, there are still many limitations in terms of methodology. For example, Nitin D. Arote's group reported a method for the efficient synthesis of brominated alkenes at room temperature in 0.5 hours using DMP / TEAB as a catalytic system and dichloroethane as a solvent. Although this reaction has the advantages of short reaction time and high yield, its substrate source is difficult, DMP needs to be specially prepared, and TEAB is highly irritating to humans, limiting the potential of this method in substrate expansion and practical application. André B. Charette's group developed a one-pot method for the conversion of benzyl bromide to brominated alkenes using CH2Br2 as a bromine source and NaHMDS as a base at -78℃. This method avoids the use of transition metal catalysts, has readily available substrates, and good functional group compatibility; however, its reaction temperature is too low and the reaction time is too long, requiring further optimization. With technological advancements, several stereoselective synthesis methods for 1,2-cis-dibromoolefins have been developed using Ag / CH3SO3H co-catalytic systems. However, this reaction, which uses terminal alkynes as raw materials and NBS as the bromine source, has limited substrate applicability.

[0004] In summary, existing methods for synthesizing brominated alkenes generally rely on reagents such as peroxides, strong bases, transition metals, or specialized ligands, often accompanied by problems such as heavy environmental burden, limited substrate availability, cumbersome procedures, numerous side reactions, or demanding conditions. Therefore, developing a simple and efficient new method for synthesizing brominated alkenes is particularly necessary. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings of existing synthetic routes by proposing a novel method for the synthesis of brominated olefin derivatives. This method uses styrene sulfoxides as substrates and metal bromides as bromine sources, achieving efficient and rapid preparation of brominated olefin derivatives under mild conditions. A significant advantage of this strategy is that it completely avoids the use of traditionally required catalysts or bromine sources such as peroxides, strong bases, transition metals, or additional ligands, thereby simplifying the reaction system and improving the practicality and environmental compatibility of the process. Specifically, the method directly converts styrene sulfoxides into the target brominated olefin compounds in the presence of metal bromides.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: Using styrene sulfoxides as substrates and metal bromides as bromine sources, the mixtures were dissolved in a reaction solvent and prepared at a certain temperature to obtain 1-bromo-2-styrene derivatives as shown in formula (1). The specific synthesis route is as follows: Where R is one of hydrogen, methyl, tert-butyl, methoxy, benzyloxy, halogen, phenyl, or naphthyl, and n is 1, 2, or 3.

[0007] Furthermore, the molar ratio of styrene sulfoxide compounds to metal bromides is 1:0.5 to 2.5.

[0008] Further, the metal bromide is one or a mixture of more of the following: copper bromide, iron bromide, manganese bromide, zinc bromide, magnesium bromide, lithium bromide, nickel bromide, cobalt bromide, cuprous bromide, and ferrous bromide. Copper bromide is preferred.

[0009] Furthermore, the reaction temperature is 25–120°C, preferably 100°C.

[0010] Furthermore, the reaction time is 3 to 48 hours, preferably 2 to 16 hours.

[0011] Furthermore, the reaction also includes post-processing, specifically: After the reaction was completed, the system was cooled to room temperature, quenched with water, extracted with ethyl acetate, and then washed with water and saturated brine, respectively. The resulting organic layer was dried, concentrated, and purified by column chromatography to obtain a pure 1-bromo-2-styrene derivative.

[0012] The reaction solvent is one or more of toluene, acetonitrile, acetone, dichloromethane, 1,2-dichloroethane, tetrahydrofuran, anhydrous ethanol, isopropanol, 1,4-dioxane, n-hexane, dimethyl sulfoxide (DMSO), and N,N-dimethylformamide (DMF), preferably DMSO.

[0013] Compared with the prior art, the beneficial effects of the present invention are: This invention provides a green, efficient, and practical method for synthesizing brominated olefin derivatives. For the first time, it utilizes styrene sulfoxide compounds as starting materials to react with metal bromide catalysts, filling a gap in the synthesis methods of brominated olefin compounds.

[0014] The method of this invention can be carried out efficiently within a mild temperature range of 25 to 120°C, without the need for extreme low or high temperature conditions, thus reducing the requirements for equipment and energy consumption. In addition, this invention does not require traditionally necessary reagents such as peroxides, strong bases, transition metal catalysts or additional ligands, which significantly simplifies the reaction system.

[0015] The present invention uses a wide range of substrates, and is compatible with mono- and poly-substituted phenylenyl sulfoxides containing electron-withdrawing or electron-donating groups, with the highest product separation yield reaching 92%. Attached Figure Description

[0016] Figure 1 In the image, (a) is the 1H NMR spectrum of 2-bromo-1-(4-chlorophenyl)ethylene prepared in Example 1, and (b) is the 1C NMR spectrum. Figure 2 In the image, (a) is the 1H NMR spectrum of 1-(2-bromovinyl)-4-methylbenzene prepared in Example 2, and (b) is the 1C NMR spectrum. Figure 3 In the image, (a) is the 1H NMR spectrum of 1-(2-bromovinyl)-4-isopropylbenzene prepared in Example 3, and (b) is the 1H NMR spectrum. Figure 4 In the image, (a) is the 1H NMR spectrum of 1-(2-bromovinyl)-2-toluene prepared in Example 4, and (b) is the 1H NMR spectrum. Figure 5 In the image, (a) is the 1H NMR spectrum of 1-(2-bromovinyl)-2-methoxybenzene prepared in Example 5, and (b) is the 1C NMR spectrum. Figure 6 In the image, (a) is the 1H NMR spectrum of 1-(2-bromovinyl)-2,4-dimethylbenzene prepared in Example 6, and (b) is the 1H NMR spectrum. Figure 7 In the image, (a) is the 1H NMR spectrum of 2-(2-bromovinyl)-1,3,5-trimethylbenzene prepared in Example 7, and (b) is the 1C NMR spectrum. Detailed Implementation

[0017] The present invention will be further described below with reference to embodiments.

[0018] As mentioned above, this invention provides a method for synthesizing 1-bromo-2-styrene derivatives via metal bromide catalysis, comprising the following steps: Using styrene sulfoxides as substrates and metal bromides as bromine sources, the mixtures were dissolved in dimethyl sulfoxide (DMSO) at a molar ratio of 1:0.5 to 2.5 and reacted at 25 to 120 °C for 3 to 48 hours. After the reaction was completed, the system was cooled to room temperature, quenched with water, extracted with ethyl acetate, and washed with water and saturated brine, respectively. The resulting organic layer was dried, concentrated, and purified by column chromatography to obtain a pure 1-bromo-2-styrene derivative as shown in formula (1). The specific synthesis route is as follows: Where R is one of hydrogen, methyl, tert-butyl, methoxy, benzyloxy, halogen, phenyl, or naphthyl, and n is 1, 2, or 3.

[0019] The metal bromide is one or a mixture of copper bromide, iron bromide, manganese bromide, zinc bromide, magnesium bromide, lithium bromide, nickel bromide, cobalt bromide, cuprous bromide, and ferrous bromide. Those skilled in the art can also select according to actual needs.

[0020] The present invention will now be described in detail. Unless otherwise specified, all raw materials used are commercially available.

[0021] Example 1: 1-Chloro-4-(2-methylsulfoxide vinyl)benzene (1.0 mmol), copper bromide (1.8 mmol), and DMSO (10.0 mL) were added to a round-bottom flask. The mixture was heated in an oil bath at 100 °C for 8 h. After the reaction was completed, the reaction solution was cooled to room temperature, quenched with 50 mL of H2O, extracted with ethyl acetate, concentrated, and then subjected to simple column chromatography (using petroleum ether as eluent at 60–90 °C) to obtain the product 2-bromo-1-(4-chlorophenyl)ethylene, with a yield of 86%.

[0022] like Figure 1 As shown in (a), the 1H NMR spectrum of 2-bromo-1-(4-chlorophenyl)ethylene prepared in Example 1: 1 H NMR (500MHz, CDCl3) δ 7.33–7.28 (m, 2H), 7.22 (d, J = 8.6 Hz, 2H), 7.06 (d, J = 14.0Hz, 1H), 6.76 (d, J = 14.0 Hz, 1H). like Figure 1 As shown in (b), the carbon spectrum of 2-bromo-1-(4-chlorophenyl)ethylene prepared in Example 1: 13 CNMR (101MHz, CDCl3) δ136.00,134.38,134.06,129.03,127.30,107.22. Example 2: 1-Methyl-4-(2-(methylsulfinyl)vinyl)benzene (1.0 mmol), copper bromide (1.8 mmol), and DMSO (10.0 mL) were added to a round-bottom flask. The mixture was heated in an oil bath at 100 °C for 8 h. After the reaction was completed, the reaction solution was cooled to room temperature, quenched with 50 mL of H2O, extracted with ethyl acetate, concentrated, and then subjected to simple column chromatography (using petroleum ether as eluent at 60–90 °C) to obtain the product 1-(2-bromovinyl)-4-methylbenzene in 89% yield.

[0023] like Figure 2 As shown in (a), the 1H NMR spectrum of 1-(2-bromovinyl)-4-methylbenzene prepared in Example 2 is as follows: 1 H NMR (500 MHz, CDCl3) δ 7.23–7.17 (m, 2H), 7.13 (d, J = 8.0 Hz, 2H), 7.07 (d, J =14.0 Hz, 1H), 6.71 (d, J = 14.0 Hz, 1H), 2.33 (s, 3H). like Figure 2 As shown in (b) above, the carbon spectrum of 1-(2-bromovinyl)-4-methylbenzene prepared in Example 2 is as follows: 13 C NMR (101MHz, CDCl3) δ138.27,137.05,133.19,129.50,128.95,126.02,105.44,21.30. Example 3: 1-Isopropyl-4-(2-(methylsulfinyl)vinyl)benzene (1.0 mmol), copper bromide (1.8 mmol), and DMSO (10.0 mL) were added to a round-bottom flask. The mixture was heated in an oil bath at 100 °C for 8 h. After the reaction was completed, the reaction solution was cooled to room temperature, quenched with 50 mL of H2O, extracted with ethyl acetate, concentrated, and then subjected to simple column chromatography (using petroleum ether as eluent at 60–90 °C) to obtain the product 1-(2-bromovinyl)-4-isopropylbenzene in 84% yield.

[0024] like Figure 3 As shown in (a), the 1H NMR spectrum of 1-(2-bromovinyl)-4-isopropylbenzene prepared in Example 3 is as follows: 1H NMR(500MHz, CDCl3) δ 7.25–7.21 (m, 2H), 7.21–7.17 (m, 2H), 7.09 (d, J = 14.0 Hz, 1H), 6.72 (d, J = 14.0Hz, 1H), 2.90 (dt, J=13.8, 6.9Hz, 1H), 1.25 (d, J = 6.9Hz, 6H). like Figure 3 As shown in (b), the carbon spectrum of 1-(2-bromovinyl)-4-isopropylbenzene prepared in Example 3 is as follows: 13 C NMR (101MHz, CDCl3) δ149.24,137.05,133.59,129.06,126.88,126.33,126.13,105.52,105.39,34.02,33.94,23.86. Example 4: 1-Methyl-2-(2-(methylsulfinyl)vinyl)benzene (1.0 mmol), copper bromide (1.8 mmol), and DMSO (10.0 mL) were added to a round-bottom flask. The mixture was heated in an oil bath at 100 °C for 8 h. After the reaction was completed, the reaction solution was cooled to room temperature, quenched with 50 mL of H2O, extracted with ethyl acetate, concentrated, and then subjected to simple column chromatography (using petroleum ether as eluent at 60–90 °C) to obtain the product 1-(2-bromovinyl)-2-toluene, with a yield of 83%.

[0025] like Figure 4 As shown in (a), the 1H NMR spectrum of 1-(2-bromovinyl)-2-toluene prepared in Example 4 is as follows: 1 H NMR(500MHz, CDCl3) δ 7.32(d, J = 5.6 Hz, 1H), 7.30 (d, J = 2.1Hz, 1H), 7.24–7.19(m, 1H), 7.19–7.12 (m, 2H), 6.64 (d, J = 13.8Hz, 1H), 2.34 (s, 3H). like Figure 4 As shown in (b) above, the carbon spectrum of 1-(2-bromovinyl)-2-toluene prepared in Example 4 is as follows: 13 CNMR(101MHz, CDCl3)135.54,135.21,135.13,130.50,128.30,126.29,108125.83,107.25,19.86. Example 5: 1-Methoxy-2-(2-(methylsulfinyl)vinyl)benzene (1.0 mmol), copper bromide (1.8 mmol), and DMSO (10.0 mL) were added to a round-bottom flask. The mixture was heated in an oil bath at 100 °C for 8 h. After the reaction was completed, the reaction solution was cooled to room temperature, quenched with 50 mL of H2O, extracted with ethyl acetate, concentrated, and then subjected to simple column chromatography (using petroleum ether as eluent at 60–90 °C) to obtain the product 1-(2-bromovinyl)-2-methoxybenzene in 80% yield.

[0026] like Figure 5 As shown in (a), the 1H NMR spectrum of 1-(2-bromovinyl)-2-methoxybenzene prepared in Example 5 is as follows: 1 H NMR(500MHz, CDCl3) δ 7.32 (d, J = 14.0 Hz, 1H), 7.29–7.25 (m, 2H), 6.93 (d, J =1.8Hz, 1H), 6.93–6.90 (m, 1H), 6.88 (dd, J = 8.8, 1.1Hz, 1H), 3.86 (s,3H). like Figure 5 As shown in (b) above, the carbon spectrum of 1-(2-bromovinyl)-2-methoxybenzene prepared in Example 5 is as follows: 13 C NMR (101MHz, CDCl3) δ156.59,133.07,129.31,128.00,124.76,120.73,110.97,107.93,55.43. Example 6: 2,4-Dimethyl-1-(2-(methylsulfinyl)vinyl)benzene (1.0 mmol), copper bromide (1.8 mmol), and DMSO (10.0 mL) were added to a round-bottom flask. The mixture was heated in an oil bath at 100 °C for 8 h. After the reaction was completed, the reaction solution was cooled to room temperature, quenched with 50 mL of H2O, extracted with ethyl acetate, concentrated, and then subjected to simple column chromatography (using petroleum ether as eluent at 60–90 °C) to obtain the product 1-(2-bromovinyl)-2,4-dimethylbenzene in 90% yield.

[0027] like Figure 6 As shown in (a), the 1H NMR spectrum of 1-(2-bromovinyl)-2,4-dimethylbenzene prepared in Example 6 is as follows: 1 HNMR (500 MHz, CDCl3) δ 7.05 (d, J = 13.9Hz, 1H), 6.94 (d, J = 9.8Hz, 3H), 6.74 (d, J = 14.0Hz, 1H), 2.33 (s, 6H). like Figure 6 As shown in (b), the carbon spectrum of 1-(2-bromovinyl)-2,4-dimethylbenzene prepared in Example 6 is as follows: 13 CNMR (101MHz, CDCl3) δ138.33,137.36,135.83,130.05,126.81,124.04,106.10,21.30. Example 7: 1,3,5-trimethyl-2-(2-(methylsulfinyl)vinyl)benzene (1.0 mmol), copper bromide (1.8 mmol), and DMSO (10.0 mL) were added to a round-bottom flask. The mixture was heated in an oil bath at 100 °C for 8 h. After the reaction was completed, the reaction solution was cooled to room temperature, quenched with 50 mL of H2O, extracted with ethyl acetate, concentrated, and then subjected to simple column chromatography (using petroleum ether as eluent at 60–90 °C) to obtain the product 2-(2-bromovinyl)-1,3,5-trimethylbenzene in 90% yield.

[0028] like Figure 7 As shown in (a), the 1H NMR spectrum of 2-(2-bromovinyl)-1,3,5-trimethylbenzene prepared in Example 7 is as follows: 1 HNMR (500MHz, CDCl3) δ7.10(d,J=14.1Hz,1H),6.87(s,2H),6.27(d,J=14.1Hz,1H),2.27(s,9H). like Figure 7 As shown in (b), the carbon spectrum of 2-(2-bromovinyl)-1,3,5-trimethylbenzene prepared in Example 7 is as follows: 13 CNMR (101MHz, CDCl3) δ137.23,135.94,135.11,132.31,128.71,108.96,21.00,20.86. Example 8: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 2-(methylsulfinylvinyl)benzene, and other conditions remained unchanged to prepare 2-bromovinylbenzene with a yield of 86%.

[0029] The 1H NMR spectrum of the 2-bromovinylbenzene prepared in Example 8: 1 H NMR (500MHz, CDCl3) δ7.25(qd,J=7.0,1.9Hz,5H),7.05(d,J=14.0Hz,1H),6.71(d,J=14.0Hz,1H). Carbon spectrum of 2-bromovinylbenzene prepared in Example 8: 13C NMR (126MHz, CDCl3) δ137.15,135.89,128.77,128.24,126.07,106.49. Example 9: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-bromo-4-(2-(methylsulfonyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-bromo-4-(2-bromovinyl)benzene in 80% yield.

[0030] The 1H NMR spectrum of 1-bromo-4-(2-bromovinyl)benzene prepared in Example 9: 1 HNMR (500MHz, CDCl3) δ7.49–7.42(m,2H),7.16(d,J=8.5Hz,2H),7.04(d,J=14.0Hz,1H),6.78(d,J=14.0Hz,1H). Carbon spectrum of 1-bromo-4-(2-bromovinyl)benzene prepared in Example 9: 13 CNMR (101MHz, CDCl3) δ136.06,134.82,131.97,131.44,130.52,127.58,122.22,107.37. Example 10: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-methoxy-4-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-4-methoxybenzene with a yield of 88%.

[0031] The 1H NMR spectrum of 1-(2-bromovinyl)-4-methoxybenzene prepared in Example 10: 1 HNMR (500MHz, CDCl3) δ7.25–7.22(m,2H),7.04(d,J=14.0Hz,1H),6.89–6.82(m,2H),6.61(d,J=14.0Hz,1H),3.81(s,3H). Carbon spectrum of 1-(2-bromovinyl)-4-methoxybenzene prepared in Example 10: 13 CNMR (101MHz, CDCl3) δ159.67,136.56,128.78,127.37,114.20,104.01,55.32. Example 11: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-ethoxy-4-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-4-ethoxybenzene with a yield of 88%.

[0032] The 1H NMR spectrum of 1-(2-bromovinyl)-4-ethoxybenzene prepared in Example 11: 1 HNMR (500MHz, CDCl3) δ7.26–7.19(m,2H),7.03(d,J=14.0Hz,1H),6.88–6.81(m,2H),6.60(d,J=13.9Hz,1H),4.03(q,J=7.0Hz,2H),1.42(t,J=7.0Hz,3H). Carbon spectrum of 1-(2-bromovinyl)-4-ethoxybenzene prepared in Example 11: 13 CNMR (101MHz, CDCl3) δ159.06,136.62,131.69,130.49,128.61,127.37,114.72,114.13,104.03,103.88,63.52,14.81. Example 12: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-isopropoxy-4-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-4-isopropoxybenzene with a yield of 82%.

[0033] The 1H NMR spectrum of 1-(2-bromovinyl)-4-isopropoxybenzene prepared in Example 12: 1 H NMR (500MHz, CDCl3) δ7.24–7.18(m,2H),7.03(d,J=13.9Hz,1H),6.86–6.81(m,2 H),6.60(d,J=13.9Hz,1H),4.55(dt,J=12.1,6.0Hz,1H),1.34(d,J=6.0Hz,6H). Carbon spectrum of 1-(2-bromovinyl)-4-isopropoxybenzene prepared in Example 12: 13 C NMR (101MHz, CDCl3) δ158.05,136.63,131.68,130.53,128.50,127.40,115.99,115.34,103.93,103.85,69.94,69.84,22.03. Example 13: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-isobutyl-4-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-4-isobutylbenzene with a yield of 92%.

[0034] The 1H NMR spectrum of 1-(2-bromovinyl)-4-isobutylbenzene prepared in Example 13: 1 HNMR (500MHz, CDCl3) δ7.24–7.19(m,2H),7.14–7.06(m,3H),6.72(d,J=13.9Hz,1H),2.45(d,J=7.2Hz,2H),1.85(dt,J=13.6,6.8Hz,1H),0.90(d,J=6.6Hz,6H). Carbon spectrum of 1-(2-bromovinyl)-4-isobutylbenzene prepared in Example 13: 13 CNMR(101MHz, CDCl3)δ142.12,137.10,133.45,129.55,128.99,128.82,125.89,105.46,45.18,30.16,22.40,22.35. Example 14: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-(tert-butyl)-4-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-4-(tert-butyl)benzene with a yield of 84%.

[0035] The 1H NMR spectrum of 1-(2-bromovinyl)-4-(tert-butyl)benzene prepared in Example 14: 1 HNMR (400MHz, CDCl3) δ7.38–7.33(m,2H),7.25(d,J=4.0Hz,2H),7.08(d,J=14.0Hz,1H),6.72(d,J=14.0Hz,1H),1.31(s,9H). Carbon spectrum of 1-(2-bromovinyl)-4-(tert-butyl)benzene prepared in Example 14: 13 CNMR (101MHz, CDCl3)δ151.48,136.94,133.20,128.80,125.86,125.74,125.18,105.64,31.22. Example 15: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 4-(2-(methylsulfinyl)vinyl)-1,1-biphenyl, and other conditions remained unchanged to prepare 4-(2-bromovinyl)-1,1-biphenyl with a yield of 84%.

[0036] The 1H NMR spectrum of 4-(2-bromovinyl)-1,1-biphenyl prepared in Example 15: 1HNMR (400MHz, CDCl3) δ7.64–7.54(m,4H),7.47(t,J=7.6Hz,2H),7.42–7.34(m,3H),7.16(d,J=14.0Hz,1H),6.83(d,J=14.0Hz,1H). Carbon spectrum of 4-(2-bromovinyl)-1,1-biphenyl prepared in Example 15: 13 CNMR (101MHz, CDCl3) δ141.05,140.42,136.81,134.93,131.98,129.54,128.94,127.62,127.51,127.11,126.99,126.61,106.65,106.48. Example 16: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-(2-(methylsulfinyl)vinyl)-4-phenoxybenzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-4-phenoxybenzene with a yield of 90%.

[0037] The 1H NMR spectrum of 1-(2-bromovinyl)-4-phenoxybenzene prepared in Example 16: 1 HNMR (500MHz, CDCl3) δ7.37–7.31(m,2H),7.28–7.23(m,2H),7.15–7.10(m,1H),7.06(d,J=13 .9Hz,1H),7.04–6.99(m,2H),6.96–6.92(m,2H),6.67(d,J=14.0Hz,1H). Carbon spectrum of 1-(2-bromovinyl)-4-phenoxybenzene prepared in Example 16: 13 CNMR (101MHz, CDCl3) δ157.53,156.69,136.37,131.02,130.63,129.88,127.55,123.70,119.40,119.24,118.84,118.13,105.34. Example 17: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-chloro-3-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-3-chlorobenzene with a yield of 82%.

[0038] The 1H NMR spectrum of 1-(2-bromovinyl)-3-chlorobenzene prepared in Example 17: 1HNMR (500MHz, CDCl3) δ7.32–7.23(m,4H),7.17(ttd,J=6.0,4.2,1.6Hz,1H),7.04(d,J=14.1Hz,1H),6.81(d,J=14.0Hz,1H). Carbon spectrum of 1-(2-bromovinyl)-3-chlorobenzene prepared in Example 17: 13 CNMR (126MHz, CDCl3) δ137.63,135.89,134.78,130.03,128.26,126.06,124.29,108.18. Example 18: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-iodo-3-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-3-iodobenzene with a yield of 78%.

[0039] The 1H NMR spectrum of 1-(2-bromovinyl)-3-iodobenzene prepared in Example 18: 1 HNMR (500MHz, CDCl3) δ7.27(t,J=7.5Hz,1H),7.20–7.16(m,2H),7.15–7.10(m,2H),6.77(d,J=14.0Hz,1H),2.91(p,J=7.0Hz,1H),1.27(d,J=6.9Hz,6H). Carbon spectrum of 1-(2-bromovinyl)-3-iodobenzene prepared in Example 18: 13 CNMR (101MHz, CDCl3) δ149.48,137.48,135.95,128.82,126.55,124.39,123.63,106.27,34.12,23.99. Example 19: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-isopropyl-3-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-3-isopropylbenzene with a yield of 82%.

[0040] The 1H NMR spectrum of 1-(2-bromovinyl)-3-isopropylbenzene prepared in Example 19: 1HNMR(400MHz, CDCl3)δ7.30(qd,J=7.8,2.8Hz,2H),7.19(d,J=14.1Hz,1H),7.14–7.02(m,2H),6.94(d,J=14.0Hz,1H). Carbon spectrum of 1-(2-bromovinyl)-3-isopropylbenzene prepared in Example 19: 13 CNMR (101MHz, CDCl3) δ130.50,129.64,127.98,124.35,116.15. Example 20: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-fluoro-2-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-2-fluorobenzene with a yield of 84%.

[0041] The 1H NMR spectrum of 1-(2-bromovinyl)-2-fluorobenzene prepared in Example 20: 1 HNMR(400MHz, CDCl3)δ7.30(qd,J=7.8,2.8Hz,2H),7.19(d,J=14.1Hz,1H),7.14–7.02(m,2H),6.94(d,J=14.0Hz,1H). Carbon spectrum of 1-(2-bromovinyl)-2-fluorobenzene prepared in Example 20: 13 CNMR (101MHz, CDCl3) δ130.50,129.64,127.98,124.35,116.15. Example 21: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 2-(2-(methylsulfinyl)vinyl)naphthalene, and other conditions remained unchanged to prepare 2-(2-bromovinyl)naphthalene with a yield of 85%.

[0042] The 1H NMR spectrum of the prepared 2-(2-bromovinyl)naphthalene in Example 21: 1 HNMR(500MHz, CDCl3)δ7.80(td,J=8.9,8.2,4.6Hz,3H),7.72–7.67(m,1H),7.47(dt,J=7.8,2.0Hz,3H),7.27(d,J=13.9Hz,1H),6.90(d,J=13.9Hz,1H). Carbon spectrum of 2-(2-bromovinyl)naphthalene prepared in Example 21: 13CNMR(101MHz, CDCl3)δ137.30,133.45,133.34,128.57,128.10,127.76,126.62,126.38,126.30,122.90,106.85. Example 22: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-(2-(methylsulfinyl)vinyl)naphthalene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)naphthalene with a yield of 74%.

[0043] The 1H NMR spectrum of 1-(2-bromovinyl)naphthalene prepared in Example 22: 1 HNMR (400MHz, CDCl3) δ8.10–8.01(m,1H),7.94–7.81(m,3H),7.63–7.48(m,3H),7.47–7.42(m,1H),6.79(d,J=13.7Hz,1H). Carbon spectrum of 1-(2-bromovinyl)naphthalene prepared in Example 22: 13 CNMR (101MHz, CDCl3) δ135.07,133.62,133.61,131.46,130.60,128.84,128.60,126. 86,126.54,126.32,126.19,126.04,125.61,125.22,124.30,124.24,123.77,108.57. Example 23: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-(benzoxy)-4-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(benzoxy)-4-(2-bromovinyl)benzene with a yield of 92%.

[0044] The 1H NMR spectrum of 1-(benzoxy)-4-(2-bromovinyl)benzene prepared in Example 23: 1 HNMR(500MHz, CDCl3)δ7.39–7.27(m,5H),7.27–7.23(m,1H),7.15(dd,J=8.7,6.5Hz, 2H),6.95(d,J=13.9Hz,1H),6.87–6.81(m,2H),6.52(d,J=13.9Hz,1H),4.97(s,2H). Example 24: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-bromo-2-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-bromo-2-(2-bromovinyl)benzene with a yield of 74%.

[0045] The 1H NMR spectrum of 1-bromo-2-(2-bromovinyl)benzene prepared in Example 24: 1 HNMR(500MHz, CDCl3)δ7.56(dd,J=8.0,1.3Hz,1H),7.44(d,J=13.9Hz,1H),7.39(dd,J= 7.8,1.7Hz,1H),7.32–7.24(m,2H),7.15(td,J=7.7,1.7Hz,1H),6.76(d,J=13.9Hz,1H). Carbon spectrum of 1-bromo-2-(2-bromovinyl)benzene prepared in Example 24: 13 CNMR (126MHz, CDCl3) δ136.23,135.98,133.16,129.59,127.67,127.12,122.76,109.22. Example 25: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-fluoro-4-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-4-fluorobenzene with a yield of 86%.

[0046] The 1H NMR spectrum of 1-(2-bromovinyl)-4-fluorobenzene prepared in Example 25: 1 HNMR (500MHz, CDCl3) δ7.30–7.24(m,2H),7.06(d,J=14.0Hz,1H),7.04–6.98(m,2H),6.69(d,J=14.0Hz,1H). Carbon spectrum of 1-(2-bromovinyl)-4-fluorobenzene prepared in Example 25: 13 CNMR (126MHz, CDCl3) δ163.61,161.64,136.00,132.18,132.15,127.76,127.69,115.90,115.73,106.12,106.10. Example 26: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-methyl-3-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-3-methylbenzene with a yield of 83%.

[0047] The 1H NMR spectrum of 1-(2-bromovinyl)-3-methylbenzene prepared in Example 26: 1 HNMR (500MHz, CDCl3) δ7.47–7.38(m,1H),7.30(d,J=9.0Hz,3H),6.95(dd,J=14.0,1.7Hz,1H),2.55(d,J=1.6Hz,3H). Carbon spectrum of 1-(2-bromovinyl)-3-methylbenzene prepared in Example 26: 13 CNMR (126MHz, CDCl3) δ138.45,137.29,135.89,129.11,128.71,126.86,123.28,106.31,21.40. Example 27: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1,2-difluoro-4-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 4-(2-bromovinyl)-1,2-difluorobenzene with a yield of 78%.

[0048] The 1H NMR spectrum of 4-(2-bromovinyl)-1,2-difluorobenzene prepared in Example 27: 1 HNMR (400MHz, CDCl3) δ7.18–7.07(m,2H),7.06–6.94(m,2H),6.75(s,1H). Carbon spectrum of 4-(2-bromovinyl)-1,2-difluorobenzene prepared in Example 27: 13 CNMR (101MHz, CDCl3) δ135.17,122.43,117.76,117.59,114.74,114.56,107.61. Example 28: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1,2-dimethyl-4-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 4-(2-bromovinyl)-1,2-dimethylbenzene with a yield of 88%.

[0049] The 1H NMR spectrum of 4-(2-bromovinyl)-1,2-dimethylbenzene prepared in Example 28: 1 HNMR (500MHz, CDCl3) δ7.10–7.07(m,2H),7.06–7.02(m,2H),6.70(d,J=13.9Hz,1H),2.25(d,J=9.1Hz,6H). Carbon spectrum of 4-(2-bromovinyl)-1,2-dimethylbenzene prepared in Example 28: 13CNMR (101MHz, CDCl3) δ137.14,136.99,133.60,132.30,130.04,129.50,127.35,126.44,123.59,105.29,105.24,19.84,19.79,19.71,19.63. Example 29: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1,3-dimethyl-5-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-3,5-dimethylbenzene with a yield of 90%.

[0050] The 1H NMR spectrum of 1-(2-bromovinyl)-3,5-dimethylbenzene prepared in Example 29: 1 HNMR (500MHz, CDCl3) δ7.03(d,J=14.0Hz,1H),6.91(d,J=9.0Hz,3H),6.72(d,J=14.0Hz,1H),2.30(s,6H). Carbon spectrum of 1-(2-bromovinyl)-3,5-dimethylbenzene prepared in Example 29: 13 CNMR (126MHz, CDCl3) δ138.31,137.34,135.82,130.01,124.00,106.05,21.24. Example 30: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-fluoro-2-methyl-4-(2-(methylsulfonyl)vinyl)benzene, and other conditions remained unchanged to prepare 4-(2-bromovinyl)-1-fluoro-2-methylbenzene with a yield of 84%.

[0051] The 1H NMR spectrum of 4-(2-bromovinyl)-1-fluoro-2-methylbenzene prepared in Example 30: 1 HNMR (500MHz, CDCl3) δ7.14–7.06(m,2H),7.03(d,J=14.0Hz,1H),6.95(t,J=8.9Hz,1H),6.67(d,J=13.9Hz,1H),2.27(d,J=2.1Hz,3H). Carbon spectrum of 4-(2-bromovinyl)-1-fluoro-2-methylbenzene prepared in Example 30: 13CNMR(101MHz,CDCl3)δ162.46,160.00,136.18,131.86,131.82,129.19,129.14, 125.41,125.23,125.12,125.04,115.51,115.29,105.74,105.71,14.59,14.55. Example 31: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 2-bromo-1-fluoro-4-(2-(methylsulfonyl)vinyl)benzene, and other conditions remained unchanged to prepare 2-bromo-4-(2-bromovinyl)-1-fluorobenzene with a yield of 76%.

[0052] The 1H NMR spectrum of 2-bromo-4-(2-bromovinyl)-1-fluorobenzene prepared in Example 31: 1 HNMR (500MHz, CDCl3) δ7.49(dd,J=8.3,7.1Hz,1H),7.08–6.99(m,2H),6.95(dd,J=8.3,2.0Hz,1H),6.83(d,J=14.0Hz,1H). Example 32: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 1-methoxy-2,3-dimethyl-4-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-4-methoxy-2,3-dimethylbenzene with a yield of 86%.

[0053] The 1H NMR spectrum of 1-(2-bromovinyl)-4-methoxy-2,3-dimethylbenzene prepared in Example 32: 1 HNMR(500MHz, CDCl3)δ7.31(dd,J=13.7,1.3Hz,1H),7.12(d,J=8.5Hz,1H),6.68(d,J=8.5Hz,1 H),6.43(dd,J=13.7,1.4Hz,1H),3.85–3.78(m,3H),2.22(d,J=1.3Hz,3H),2.16(d,J=1.3Hz,3H). Carbon spectrum of 1-(2-bromovinyl)-4-methoxy-2,3-dimethylbenzene prepared in Example 32: 13 CNMR (101MHz, CDCl3) δ157.61,136.46,135.19,132.96,128.43,126.93,125.39,124.47,107.90,105.27,55.55,16.09,11.95. Example 33: In Example 1, 1-chloro-4-(2-methylsulfonylvinyl)benzene was replaced with 2-methoxy-1,3-dimethyl-5-(2-(methylsulfinyl)vinyl)benzene, and other conditions remained unchanged to prepare 5-(2-bromovinyl)-2-methoxy-1,3-dimethylbenzene with a yield of 86%.

[0054] The 1H NMR spectrum of 5-(2-bromovinyl)-2-methoxy-1,3-dimethylbenzene prepared in Example 33: 1 HNMR (500MHz, CDCl3) δ7.00(d,J=13.9Hz,1H),6.96(s,2H),6.65(d,J=13.9Hz,1H),3.72(s,3H),2.29(s,6H). Carbon spectrum of 5-(2-bromovinyl)-2-methoxy-1,3-dimethylbenzene prepared in Example 33: 13 CNMR (101MHz, CDCl3) δ157.21,136.74,131.55,131.29,129.67,126.65,105.12,59.70,16.14. Example 34: In Example 10, copper bromide was replaced with manganese bromide, and other conditions remained unchanged to prepare 1-(2-bromovinyl)-4-methoxybenzene with a yield of 81%.

[0055] Example 35: Replacing copper bromide with boron bromide in Example 10, while keeping other conditions unchanged, yielded 1-(2-bromovinyl)-4-methoxybenzene in 42% yield. Example 36: In Example 10, the amount of copper bromide added was changed to 2.5 mmol, and the solvent DMSO was replaced with DMF. With other conditions unchanged, 1-(2-bromoethene)-4-methoxybenzene was prepared with a yield of 83%.

[0056] Example 37: In Example 10, the amount of copper bromide added was changed to 0.5 mmol, and the solvent DMSO was replaced with DMF. With other conditions unchanged, 1-(2-bromoethene)-4-methoxybenzene was prepared with a yield of 53%.

[0057] Example 38: In Example 10, copper bromide was replaced with a mixture of copper bromide and cuprous bromide, the amount of copper bromide added was changed to 1.5 mmol, the amount of cuprous bromide added was changed to 1 mmol, the solvent DMSO was replaced with DMF, and other conditions remained unchanged, 1-(2-bromoethene)-4-methoxybenzene was prepared with a yield of 41%.

[0058] Example 39: In Example 10, the amount of copper bromide added was changed to 0.5 mmol, and the solvent DMSO was replaced with acetone. With other conditions unchanged, 1-(2-bromoethene)-4-methoxybenzene was prepared with a yield of 40%.

[0059] Example 40: In Example 10, the amount of copper bromide added was changed to 2.5 mmol, the solvent DMSO was replaced with DMF, the temperature was changed from 100 ℃ to 50 ℃, and other conditions remained unchanged, 1-(2-bromoethene)-4-methoxybenzene was prepared with a yield of 50%.

[0060] Example 41: In Example 10, the amount of copper bromide added was changed to 2.5 mmol, the solvent DMSO was replaced with acetone, the temperature was changed from 100℃ to 120℃, and other conditions remained unchanged, 1-(2-bromoethene)-4-methoxybenzene was prepared with a yield of 74%.

[0061] Example 42: In Example 10, the amount of copper bromide added was changed to 2.5 mmol, the solvent DMSO was replaced with DMF, the temperature was changed from 100 ℃ to 90 ℃, and the reaction time was changed to 14 hours. Other conditions remained unchanged, and 1-(2-bromoethene)-4-methoxybenzene was prepared with a yield of 85%.

[0062] Example 43: In Example 10, the amount of copper bromide added was changed to 2.5 mmol, the solvent DMSO was replaced with DMF, the temperature was changed from 100 ℃ to 110 ℃, and the reaction time was changed to 36 hours. Other conditions remained unchanged, and 1-(2-bromoethene)-4-methoxybenzene was prepared with a yield of 88%.

[0063] In summary, this invention develops a method for preparing brominated olefin derivatives by directly reacting alkenyl sulfoxide compounds as starting materials with metal bromides as bromine sources. Compared with existing synthetic methods, this invention completely avoids the use of peroxides, strong bases, transition metals, or additional ligands as catalysts or bromine sources, and has outstanding advantages such as simple post-processing and mild reaction conditions. It is a concise, efficient, highly selective, and environmentally friendly new strategy for the synthesis of brominated olefin derivatives.

[0064] The above embodiments are not intended to limit the present invention, and the present invention is not limited to the above embodiments. Any embodiment that meets the requirements of the present invention is within the protection scope of the present invention.

Claims

1. A method for synthesizing 1-bromo-2-styrene derivatives via metal bromide catalysis, characterized in that, The method includes the following steps: Using styrene sulfoxides as substrates and metal bromides as bromine sources, the mixtures were dissolved in a solvent and prepared at a certain temperature to obtain 1-bromo-2-styrene derivatives as shown in formula (1). The synthesis route is as follows: Where R is one of hydrogen, methyl, tert-butyl, methoxy, benzyloxy, halogen, phenyl, or naphthyl, and n is 1, 2, or 3.

2. The method according to claim 1, characterized in that, The molar ratio of styrene sulfoxides to metal bromides is 1:0.5 to 2.

5.

3. The method according to claim 1, characterized in that, The metal bromide is one or a mixture of multiple of the following: copper bromide, iron bromide, manganese bromide, zinc bromide, magnesium bromide, lithium bromide, nickel bromide, cobalt bromide, cuprous bromide, and ferrous bromide.

4. The method according to claim 1, characterized in that, The reaction temperature is 25–120℃.

5. The method according to claim 1, characterized in that, The reaction time is 3 to 48 hours.

6. The method according to claim 1, characterized in that, The reaction also includes post-processing, specifically: After the reaction was completed, the system was cooled to room temperature, quenched with water, extracted with ethyl acetate, and then washed with water and saturated brine, respectively. The resulting organic layer was dried, concentrated, and purified by column chromatography to obtain a pure 1-bromo-2-styrene derivative.

7. The method according to claim 1, characterized in that, The reaction solvent is one or more of toluene, acetonitrile, acetone, dichloromethane, 1,2-dichloroethane, tetrahydrofuran, anhydrous ethanol, isopropanol, 1,4-dioxane, n-hexane, dimethyl sulfoxide, and N,N-dimethylformamide.

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