Synthesis method of photocatalytic asymmetric thioether compound

Abstract

The invention belongs to the technical field of organic synthetic chemistry, and particularly relates to a method for synthesizing a photocatalytic asymmetric thioether compound. According to the invention, alkyl halide is taken as an initial raw material, a ruthenium complex is taken as a photocatalyst, phenylthiotrimethylsilane is taken as a sulfur source, cross coupling of C-S bonds under a photocatalytic condition is realized in an inert gas atmosphere through blue light irradiation, and a series of asymmetric thioether compounds are obtained at high yield. The synthesis method provided by the invention has the characteristics of greenness, environmental protection, mild conditions, high yield and the like. The asymmetric thioether compound disclosed by the invention is widely applied to the fields of medicines, pesticides, materials and the like, and the synthesis method provides a widely applicable preparation method for the compound.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthetic chemistry, and in particular relates to a method for synthesizing a photocatalytic asymmetric sulfide compounds. Background Art

[0002] Thioethers are a very valuable class of compounds that are widely found in materials, bioactive molecules, medicines, and agrochemicals. For example, cimetidine is a drug for the treatment of gastric ulcers and is also valuable in tumor immunity. Sindhan was originally developed for the treatment of mental illness and has shown its value in anti-coronavirus. Imipenem is clinically used for respiratory tract infections, urinary tract infections, and abdominal infections caused by Gram-positive bacteria, Gram-negative bacteria, and anaerobic bacteria. Thioether compounds are also effective ligands for metal complexes. As structurally stable and readily available compounds, thioethers have been shown to be an effective class of electrophilic reagents that can cross-couple with a series of organometallic reagents, such as organomagnesium, organozinc, organostannanes, and organoboronic acids. Therefore, the synthesis of thioether compounds has always received widespread attention, and it is of great significance to find green and efficient synthesis methods.

[0003]

[0004] One of the classic methods for preparing thioethers is to construct a CS bond by transition metal-catalyzed nucleophilic substitution of halogenated aromatic hydrocarbons with thiophenols / alcohols. In 1978, Migita et al. first reported a method for preparing aryl thioethers by reacting aryl halides with thiophenols (alcohols) catalyzed by tetrakis(triphenylphosphine)palladium (Chem. Lett. 1978, 7(1), 13-14). In 2004, Taniguchi et al. reported a method for preparing asymmetric thioethers by nickel-catalyzed reaction of aryl iodides and disulfides (J. Org. Chem. 2004, 69(20), 6904-6906). This reaction has good compatibility with aryl iodides substituted with various functional groups. In 2022, Lv Guifen's research group used nickel-catalyzed CS reductive cross-coupling of alkyl halides and arylthiosilanes to prepare alkyl aryl thioethers (Org. Lett. 2022, 24(28), 5115-5119). This method utilizes a nonpolar transformation strategy of arylthiosilanes and Ni reduction catalysis to enable the conversion of various alkyl halides into alkylaryl sulfides, which is a conceptually new C(sp 3 )-S reductive cross-coupling pathway has a broad substrate range, excellent functional group compatibility and chemical selectivity, and has important applications in the late-stage modification of bio-related molecules.

[0005]

[0006] In addition to transition metal catalysis, acids, bases, etc. can also promote the synthesis of thioethers. In 2010, Bolm et al. reported a method for synthesizing thioether compounds from aromatic halides and thiophenols (alcohols) under transition metal-free conditions (Adv. Synth. Catal. 2010, 352 (17), 2892-2898). In 2023, Bi Xiaojing's research group developed an effective HI-promoted CS bond formation strategy for the synthesis of various asymmetric thioethers from sodium sulfinate and electron-rich aromatics (J. Org. Chem. 2023, 88, 4092-4100). The reaction has a wide substrate range and good functional group tolerance. The reaction is carried out under mild conditions and the target product is obtained with good to excellent yields.

[0007]

[0008] Electrochemical synthesis is a green and environmentally friendly method. In 2020, Ackermann's group proposed an efficient and mild electroreduction sulfurization method (Chem. Eur. J. 2021, 27, 4883-4887). Through electrophilic cross-coupling of alkyl bromides with stable thiosulfonates, alkyl sulfides were obtained with excellent yields and broad functional group tolerance in the absence of irritating chemical reducing agents.

[0009]

[0010] In summary, various methods for preparing sulfide compounds from halogenated hydrocarbons have been reported in the literature. However, the above methods have problems such as the need to add excessive metal reducing agents, acids, bases, too high reaction temperatures, or the need for external electrochemical equipment. Therefore, it is necessary to find a new method for synthesizing alkyl sulfide compounds that is more efficient and more controllable to overcome the above technical problems. Summary of the invention

[0011] The technical problem to be solved by the present invention is to provide a simple, efficient, environmentally friendly and highly atom-economical synthesis method to address the problems of the need to add excessive metal reducing agents, acids, bases, too high reaction temperatures or the need for external electrochemical equipment in the synthesis of sulfide compounds.

[0012] The technical solution adopted by the present invention is as follows:

[0013] In a first aspect, the present invention provides a method for synthesizing a photocatalytic asymmetric sulfide compound, wherein the reaction steps of the synthesis method are as follows: uniformly mixing a halide, phenylthiotrimethylsilane, a photocatalyst, and an organic solvent, irradiating with blue light under an inert gas atmosphere until the reaction is complete, and obtaining an asymmetric sulfide compound;

[0014] The reaction equation of the synthesis method is shown in Formula I:

[0015]

[0016] In Formula I, R includes substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted boric acid pinacol ester, substituted or unsubstituted carbonyl, substituted or unsubstituted ester, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclic group;

[0017] X is a halogen atom;

[0018] The photocatalyst is selected from any one of tris(1,10-phenanthroline)ruthenium(II)bis(hexafluorophosphate)[Ru(phen)3(PF6)2], terpyridyl ruthenium chloride hexahydrate[Ru(bpy)3Cl2 6H2O], and dichlorotris(1,10-phenanthroline)ruthenium(II)[Ru(phen)3Cl2];

[0019] Preferably, the halide is selected from any one of benzyl bromide, 4-methylbenzyl bromide, 4-fluorobenzyl bromide, 1-bromoethylbenzene, 2-bromoethylbenzene, 1-(2-bromoethyl)-4-methylbenzene, 1-(2-bromoethyl)-4-fluorobenzene, 3-bromopropylbenzene, 1-bromopentane, 1-bromo-5-chloropentane, 2-bromoethylcyclohexane, 2-bromoethylcyclopropane, 3-bromopropylboronic acid pinacol ester, 1-bromo-3,3-dimethyl-2-butanone, ethyl 4-bromobutyrate, cinnamyl bromide, 4'-bromomethyl-2-methylformate biphenyl, 1,5-dibromopentane, and N-Boc-3-iodo-L-alanine methyl ester.

[0020] Preferably, the molar ratio of the halide to phenylthiotrimethylsilane is 1:1.1-2.5.

[0021] Preferably, the reaction temperature is 10-30°C.

[0022] Preferably, the reaction time is 20 to 28 hours.

[0023] Preferably, the amount of the reaction photocatalyst is 1 to 2.5 mol%.

[0024] Preferably, the blue light wavelength is 440-465 nm.

[0025] Preferably, the organic solvent is N,N-dimethylformamide or N,N-dimethylacetamide.

[0026] Preferably, the obtained product is extracted three times by adding ethyl acetate and saturated sodium carbonate aqueous solution, and the organic phases are combined, dried, and separated by column chromatography to obtain a pure product.

[0027] In a second aspect, the present invention provides an asymmetric sulfide compound prepared by the method described in the first aspect.

[0028] Preferably, the thioether compound specifically includes the following compounds:

[0029]

[0030] Beneficial effects of the present invention: The present invention uses alkyl halide as substrate, phenylthiotrimethylsilane as sulfur source, [Ru(phen)3(PF6)2], [Ru(bpy)3Cl2 6H2O], [Ru(phen)3Cl2] as photocatalyst, and obtains a series of asymmetric sulfide compounds in high yield under 440-465nm blue light irradiation at 10-30°C. Compared with the prior art, the advantages of the synthesis method of the present invention are as follows:

[0031] (1) The present invention uses alkyl halides as substrates, which are cheap and readily available;

[0032] (2) The reaction mode of the synthesis method of the present invention is photocatalysis, which is green and environmentally friendly and has mild conditions;

[0033] (3) The method of the present invention uses a small amount of catalyst and has extremely high catalytic efficiency;

[0034] (4) The synthesis method of the present invention has a simple reaction system and is easy to operate;

[0035] (5) The synthetic method of the present invention has high yield and a wide range of substrate applications.

[0036] The thioether compounds efficiently synthesized by the present invention are important skeletons of many drugs and bioactive molecules. The synthesis method of the present invention provides a widely applicable preparation method for the synthesis of such compounds. DETAILED DESCRIPTION

[0037] Example 1

[0038] Synthesis of (3a) using benzyl bromide (1a) and phenylthiotrimethylsilane (2) as raw materials:

[0039]

[0040] Benzyl bromide (1a) (0.6 mmol), phenylthiotrimethylsilane (2) (0.66 mmol), Ru(phen)3(PF6)2 (1 mol%), DMF (6 mL) were added to a 10 mL reaction tube, filled with nitrogen, irradiated with 465 nm blue light, and the temperature was controlled to 10°C to react until the substrate completely disappeared (TLC monitoring, 24 h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 89%.

[0041] 1H NMR (300MHz, CDCl3) δ7.37-7.19(m,9H),7.18-7.09(m,1H),4.08(s,2H). 13 CNMR(75MHz, CDCl3)δ=137.49,136.45,129.81,128.91,128.89,128.56,127.24,126.38,39.04.

[0042] Example 2

[0043] Synthesis of (3b) using 4-methylbenzyl bromide (1b) and phenylthiotrimethylsilane (2) as raw materials:

[0044]

[0045] 0.6mmol 4-methylbenzyl bromide (1b), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3Cl2 (1.5mol%), DMA (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 20°C to react until the substrate completely disappeared (TLC monitoring, 20h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 94%.

[0046] 1 H NMR (300MHz, CDCl3) δ7.48-7.27(m,7H),7.21(d,J=7.9Hz,2H),4.21(s,2H),2.44(s, 3H).136.82,136.73,134.32,129.53,129.24,128.85,128.76,126.18,38.61,21.17.

[0047] Example 3

[0048] Synthesis of (3c) using 4-fluorobenzyl bromide (1c) and phenylthiotrimethylsilane (2) as raw materials:

[0049]

[0050] 0.6mmol 4-fluorobenzyl bromide (1c), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1.5mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 30°C to react until the substrate completely disappeared (TLC monitoring, 28h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 93%.

[0051] 1 H NMR (300MHz, CDCl3) δ7.56-7.21 (m, 7H), 7.05 (t, J = 8.7Hz, 2H), 4.16 (s, 2H). 13 CNMR (75MHz, CDCl3) δ162.03 (d, J = 245.6Hz), 135.96, 133.33 (d, J = 3.2Hz), 130.45 (d, J = 8.1Hz), 130.20, 128.99, 126.66, 115.41 (d, J = 21.5Hz), 38.45.

[0052] Example 4

[0053] Synthesize (3d) from 1-bromoethylbenzene (1d) and phenylthiotrimethylsilane (2):

[0054]

[0055] 0.6 mmol 1-bromoethylbenzene (1d), 0.75 mmol phenylthiotrimethylsilane (2), Ru(bpy)3Cl 2. 6H2O (1.5 mol%) and DMF (6 mL) were added to a 10 mL reaction tube, filled with nitrogen, irradiated with 440 nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24 h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 81%.

[0056] 1 H NMR (300MHz, CDCl3) δ7.38 (m, 6H), 7.29 (m, 4H), 4.44 (q, J = 7.0Hz, 1H), 1.73 (d, J = 7.0Hz, 3H). 13 C NMR (75MHz, CDCl3) δ143.30,135.21,132.58,128.79,128.50,127.39,127.25,127.23,48.08,22.44.

[0057] Example 5

[0058] Synthesis of (3e) using 2-bromoethylbenzene (1e) and phenylthiotrimethylsilane (2) as raw materials:

[0059]

[0060] 0.6mmol 2-bromoethylbenzene (1e), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 85%.

[0061] 1 H NMR (300MHz, CDCl3) δ7.60-7.18(m,10H),3.27(dd,J=9.2,6.5Hz,2H),3.03(dd,J=9.0,6.7Hz,2H). 13 C NMR (75MHz, CDCl3) δ140.30,136.46,129.27,129.04,128.61,126.56,126.07,35.72,35.17.

[0062] Example 6

[0063] Synthesis of (3f) using 1-(2-bromo-ethyl)-4-methylbenzene (1f) and phenylthiotrimethylsilane (2) as raw materials:

[0064]

[0065] 0.6mmol 1-(2-bromo-ethyl)-4-methylbenzene (1f), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 86%.

[0066] 1 H NMR (300MHz, CDCl3) δ7.30(m,4H),7.21-6.96(m,5H),3.12(m,2H),2.94-2.76(m,2H),2.30(s,3H). 13 C NMR (75MHz, CDCl3) δ = 137.22, 136.54, 136.05, 129.28, 129.16, 129.00, 128.47, 125.97, 35.23, 21.16.

[0067] Example 7

[0068] Synthesized from 1-fluoro-4-(2-bromoethyl)benzene (1g) and phenylthiotrimethylsilane (2) (3g):

[0069]

[0070] 0.6mmol 1-fluoro-4-(2-bromoethyl)benzene (1g), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 83%.

[0071] 1 H NMR (300MHz, CDCl3) δ7.23 (m, 4H), 7.07 (m, 3H), 6.88 (t, J = 8.7Hz, 2H), 3.04 (m, 2H), 2.89-2.66 (m, 2H). 13 C NMR (75MHz, CDCl3) δ = 161.67 (d, J = 244.3), 136.25, 135.90 (d, J = 3.2), 130.06 (d ,J=7.9),129.38,129.07,126.19,115.36(d,J=21.2),35.32(d,J=1.2),34.84.

[0072] Example 8

[0073] Synthesized from 3-bromopropylbenzene (1h) and phenylthiotrimethylsilane (2) (3h):

[0074]

[0075] 0.6mmol 3-bromopropylbenzene (1h), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 78%.

[0076] 1H NMR (300MHz, CDCl3) δ7.36-6.90(m,10H),2.82(t,J=7.3Hz,2H),2.66(t,J=7.5Hz,2H),1.94-1.80(m,2H). 13 C NMR (75MHz, CDCl3) δ = 141.38, 136.65, 129.18, 128.96, 128.60, 128.50, 126.08, 125.91, 34.76, 32.94, 30.71.

[0077] Example 9

[0078] Synthesis of (3i) using 1-bromopentane (1i) and phenylthiotrimethylsilane (2) as raw materials:

[0079]

[0080] 0.6mmol 1-bromopentane (1i), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 79%.

[0081] 1 H NMR (300MHz, CDCl3) δ7.32(m,4H),7.19(m,1H),3.08-2.83(m,2H),1.83-1.62(m,2H),1.51-1.22(m,4H),0.93(t,J=7.1Hz,3H). 13 C NMR (75MHz, CDCl3) δ = 137.16, 128.95, 128.92, 125.75, 33.65, 31.16, 28.97, 22.40, 14.12.

[0082] Example 10

[0083] Synthesized from 1-bromo-5-chloropentane (1 g) and phenylthiotrimethylsilane (2) (3 g):

[0084]

[0085] 0.6mmol 1-bromo-5-chloropentane (1g), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 72%.

[0086] 1 H NMR (300MHz, CDCl3) δ7.35-7.21(m,4H),7.20-7.11(m,1H),3.49(t,J=6.6Hz,2H),2.90(t,J=7.1Hz,2H),1.81-1.49(m,6H). 13 C NMR (75MHz, CDCl3) δ = 136.64, 129.05, 128.91, 125.86, 44.85, 33.41, 32.14, 28.43, 26.07.

[0087] Embodiment 11

[0088] Synthesis (3k) using 2-cyclohexylethyl bromide (1k) and phenylthiotrimethylsilane (2) as raw materials:

[0089]

[0090] 0.6mmol 2-cyclohexylbromoethane (1k), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 76%.

[0091] 1 H NMR (300MHz, CDCl3) δ7.35-7.15(m,4H),7.09(m,1H),2.94-2.76(m,2H),1.64(m,5H) ),1.47(dd,J=15.0,7.1Hz,2H),1.32(m,1H),1.22-1.07(m,3H),0.91-0.74(m,3H). 13C NMR (75MHz, CDCl3) δ = 137.23, 128.95, 128.75, 125.68, 37.11, 36.75, 33.14, 31.21, 26.67, 26.35.

[0092] Example 12

[0093] Synthesize (3l) using 2-bromoethylcyclopropane (1l) and phenylthiotrimethylsilane (2) as raw materials:

[0094]

[0095] 0.6mmol 2-bromoethylcyclopropane (1l), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 73%.

[0096] 1 H NMR(300MHz, CDCl3)δ7.24(m,4H),7.10(dd,J=9.9,4.2Hz,1H),3.05-2.86(m,2H),1 .48(dd,J=14.8,7.2Hz,2H),0.75(m,1H),0.40(dt,J=8.0,5.0Hz,2H),0.03(s,2H). 13 C NMR (75MHz, CDCl3) δ = 137.09, 128.92, 128.82, 125.71, 34.55, 33.53, 10.54, 4.63.

[0097] Embodiment 13

[0098] Synthesize (3m) from 3-bromopropylboronic acid pinacol ester (1m) and phenylthiotrimethylsilane (2):

[0099]

[0100] 0.6mmol 3-bromopropylboronic acid pinacol ester (1m), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 62%.

[0101] 1 H NMR (300MHz, CDCl3) δ7.30-7.13(m,4H),7.06(t,J=7.2Hz,1H),2.95-2.67(m,2H),1.81-1.55(m,2H),1.16(s,12H),0.85(t,J=7.7Hz,2H). 13 C NMR (75MHz, CDCl3) δ = 137.21, 128.86, 128.63, 125.51, 83.19, 35.59, 24.93, 24.04.

[0102] Embodiment 14

[0103] Synthesize (3n) from 1-bromo-3,3-dimethyl-2-butanone (1n) and phenylthiotrimethylsilane (2):

[0104]

[0105] 0.6mmol 1-bromo-3,3-dimethyl-2-butanone (1n), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 91%.

[0106] 1 H NMR (300MHz, CDCl3) δ7.49-7.42(m,2H),7.41-7.27(m,3H),4.05(s,2H),1.27(s,9H). 13 C NMR (75MHz, CDCl3) δ = 209.42, 135.47, 130.01, 128.92, 126.65, 44.23, 40.53, 26.55.

[0107] Embodiment 15

[0108] Synthesis of (3o) using ethyl 4-bromobutyrate (1o) and phenylthiotrimethylsilane (2) as raw materials:

[0109]

[0110] 0.6mmol ethyl 4-bromobutyrate (1o), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 78%.

[0111] 1 H NMR (300MHz, CDCl3) δ7.22(m,4H),7.10(t,J=7.1Hz,1H),4.05(q,J=7.1Hz,2H),2.89 (t,J=7.2Hz,2H),2.38(t,J=7.2Hz,2H),1.88(p,J=7.2Hz,2H),1.17(t,J=7.1Hz,3H). 13 C NMR (75MHz, CDCl3) δ = 173.05, 136.15, 129.35, 129.01, 126.10, 60.52, 32.98, 24.43, 14.31.

[0112] Example 16

[0113] Synthesized from cinnamyl bromide (1p) and phenylthiotrimethylsilane (2) (3p):

[0114]

[0115] 0.6mmol cinnamyl bromide (1p), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 84%.

[0116] 1H NMR (300MHz, CDCl3) δ7.39-7.25(m,2H),7.23-7.01(m,8H),6.33(d,J=15.7Hz,1H),6.15(dt,J=15.6,7.0Hz,1H),3.60(dd,J=7.0,0.6Hz,2H). 13 C NMR (75MHz, CDCl3) δ = 136.81, 135.94, 132.86, 130.31, 128.94, 128.62, 127.66, 126.49, 126.43, 125.13, 37.18.

[0117] Embodiment 17

[0118] Synthesized from 4'-bromomethyl-2-methylformate biphenyl (1q) and phenylthiotrimethylsilane (2) as raw materials (3q):

[0119]

[0120] 0.6mmol 4'-bromomethyl-2-formyl biphenyl (1q), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 82%.

[0121] 1 H NMR (300MHz, CDCl3) δ7.72-7.61(m,1H),7.31(td,J=7.5,1.3Hz,1H),7.24-7.12(m,6H),7.12-6.94(m,5H),3.98(s,2H),3.41(s,3H). 13 C NMR(75MHz, CDCl3)δ=168.94,141.86,140.05,136.35,136.21,131.15,130.74, 130.50,129.67,129.63,128.73,128.47,128.32,127.07,126.19,51.73,38.51.

[0122] Embodiment 18

[0123] Synthesis of (3r) using 1,5-dibromopentane (1r) and phenylthiotrimethylsilane (2) as raw materials:

[0124]

[0125] 0.6mmol 1,5-dibromopentane (1r), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 63%.

[0126] 1 H NMR (300MHz, CDCl3) δ7.34 (m, 8H), 7.25-7.15 (m, 2H), 2.94 (t, J = 7.0Hz, 4H), 1.89-1.51 (m, 6H). 13 C NMR (75MHz, CDCl3) δ = 136.73, 128.93, 128.85, 125.74, 33.35, 28.62, 27.86.

[0127] Embodiment 19

[0128] Synthesized from N-Boc-3-iodo-L-alanine methyl ester (1s) and phenylthiotrimethylsilane (2) (3s):

[0129]

[0130] 0.6mmol N-Boc-3-iodo-L-alanine methyl ester (1s), 0.75mmol phenylthiotrimethylsilane (2), Ru(phen)3(PF6)2 (1mol%), DMF (6mL) were added to a 10mL reaction tube, filled with nitrogen, irradiated with 440nm blue light, and the temperature was controlled to 25°C to react until the substrate completely disappeared (TLC monitoring, 24h). Ethyl acetate and saturated sodium carbonate aqueous solution were added for extraction three times, the organic phases were combined, dried, and separated by column chromatography to obtain a light yellow oily liquid with a yield of 45%.

[0131] 1 H NMR (300 MHz, CDCl3) δ7.41 (d, J = 7.3 Hz, 2H), 7.25 (m, 3H), 5.37 (d, J = 7.7 Hz, 1H), 4.56 (dd, J = 8.1, 4.3 Hz, 1H), 3.53 (s, 3H), 3.38 (d, J = 4.6 Hz,2H),1.42(s,9H). 13C NMR(75 MHz,CDCl3)δ=171.15,155.11,134.84,131.19,129.15,127.18,80.26,53.36,52.47,37.37,28.39.

Claims

1. A method for synthesizing a photocatalytic asymmetric sulfide compound, characterized in that: The synthesis method comprises the following steps: uniformly mixing a halide, phenylthiotrimethylsilane, a photocatalyst and an organic solvent, irradiating with blue light under an inert gas atmosphere until the reaction is complete, and obtaining an asymmetric sulfide compound; The reaction equation of the synthesis method is shown in Formula I: In Formula I, R includes substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted boric acid pinacol ester, substituted or unsubstituted carbonyl, substituted or unsubstituted ester, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclic group; X is a halogen atom; The photocatalyst is selected from any one of tris(1,10-phenanthroline)ruthenium(II)bis(hexafluorophosphate) [Ru(phen)3(PF6)2], terpyridine ruthenium chloride hexahydrate [Ru(bpy)3Cl2 6H2O], and dichlorotris(1,10-phenanthroline)ruthenium(II) [Ru(phen)3Cl2].

2. The method for synthesizing a photocatalytic asymmetric sulfide compounds according to claim 1, characterized in that: The halide is selected from any one of benzyl bromide, 4-methylbenzyl bromide, 4-fluorobenzyl bromide, 1-bromoethylbenzene, 2-bromoethylbenzene, 1-(2-bromoethyl)-4-methylbenzene, 1-(2-bromoethyl)-4-fluorobenzene, 3-bromopropylbenzene, 1-bromopentane, 1-bromo-5-chloropentane, 2-bromoethylcyclohexane, 2-bromoethylcyclopropane, 3-bromopropylboronic acid pinacol ester, 1-bromo-3,3-dimethyl-2-butanone, ethyl 4-bromobutyrate, cinnamyl bromide, 4'-bromomethyl-2-methylformate biphenyl, 1,5-dibromopentane, and N-Boc-3-iodo-L-alanine methyl ester.

3. The method for synthesizing a photocatalytic asymmetric sulfide compounds according to claim 1, characterized in that: The molar ratio of the halide to phenylthiotrimethylsilane is 1:1.1-2.

5.

4. The method for synthesizing a photocatalytic asymmetric sulfide compounds according to claim 1, characterized in that: The reaction temperature is 10-30°C.

5. The method for synthesizing photocatalytic asymmetric sulfide compounds according to claim 1, characterized in that: The reaction time is 20 to 28 hours.

6. The method for synthesizing a photocatalytic asymmetric sulfide compounds according to claim 1, characterized in that: The dosage of the reaction photocatalyst is 1 to 2.5 mol%.

7. The method for synthesizing a photocatalytic asymmetric sulfide compounds according to claim 1, characterized in that: The wavelength of the blue light is 440-465 nm.

8. The method for synthesizing photocatalytic asymmetric sulfide compounds according to claim 1, characterized in that: The organic solvent is N,N-dimethylformamide or N,N-dimethylacetamide.

9. An asymmetric sulfide compound prepared by the method according to any one of claims 1 to 8.

10. The asymmetric sulfide compound according to claim 9, characterized in that: The thioether compounds specifically include the following compounds:

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