Catalyst-free light-driven synthesis method for sulfonamide compounds

Abstract

The invention discloses a catalyst-free light-driven synthesis method for sulfonamide compounds, which is widely applied to the fields of organic synthesis, pesticides, medicines, material science and the like. According to the invention, alkyl alcohol and sulfinyl imide are taken as reactants, and a deoxidation alkylation reaction is carried out only under the driving of blue light, so that a series of sulfinamide derivatives with diversified functional groups are synthesized. In the reaction, alcohol serves as an alkyl source, belongs to a bulk chemical and has the advantages of being wide in source and easy to obtain; in addition, visible light is adopted as the only driving force of the reaction, and expensive photocatalysts are not needed, so that the whole reaction process is more green and efficient. The method provides a new thought for efficient synthesis of sulfinamide, has the characteristics of mild reaction conditions, convenience in experimental operation, good substrate compatibility and easiness in scale enlargement, and has relatively high application value and social and economic benefits.

Description

Technical Field

[0001] The invention relates to a method for preparing a pharmaceutical chemical intermediate, in particular to a method for generating sulfenamide by reacting alcohol deoxygenation and sulfenyl imine driven by light without a catalyst. Background Art

[0002] Sulfenamide is an important class of sulfur-containing compounds, which are widely used in organic synthesis, pesticides, medicine and materials science. In organic synthesis, sulfenamide is an important intermediate for the generation of sulfur-containing compounds such as sulfonamide, sulfoximine, sulfonyl imide amide and sulfonyl imide ester. At the same time, sulfenamide has a chiral sulfur atom and stable conformation, which is an important tool in asymmetric synthesis. In addition, the sulfenamide skeleton is also an important pharmacophore, accounting for up to 10% of FDA-approved drugs, and is widely present in anti-tumor, antiviral and other drugs.

[0003] The traditional synthetic route of sulfenamide mainly relies on the nucleophilic substitution reaction of amine and sulfenyl chloride (Furukawa, M.; Okawara, T. Convenient Syntheses of Sulfinamide Derivatives. Synthesis 1976, 1976, 339-340). In recent years, the coupling reaction of arylboronic acid and DAST type reagent and copper-mediated transsulfenamidation reaction have also been developed (Wang, Q.; Tang, X.; Shi, M. Metal-Free Cross-Coupling of Arylboronic Acids and Derivatives with DAST-Type Reagents for Direct Access to Diverse Aromatic Sulfinamides and Sulfonamides. Angew. Chem. Int. Ed., 2016, 55, 10811-10815.). However, the above-mentioned synthesis methods generally have disadvantages such as difficult to obtain reagents, instability, complex reaction systems, and harsh reaction conditions. There is an urgent need to develop a new method with simple and easy-to-obtain raw materials, mild reaction conditions, and good functional group compatibility.

[0004] The present invention is inspired by a paper published in the Journal of the American Chemical Society in 2023 by the Michael C Willis group of the University of Oxford, UK (Jonathan AA; Jagadeesh K.; Christopher FP; Darren LP; Kirsten EC; and Michael CW, Photocatalytic Carboxylate to Sulfinamide Switching Delivers a Divergent Synthesis of Sulfonamides and Sulfonimidamides. J. Am. Chem. Soc., 2023, 145 (39), 21623-21629.). The method uses readily available and structurally diverse alkyl carboxylic acids as starting materials, utilizes an acridine photocatalyst and 400 nm light to generate alkyl radicals from carboxylic acids, and then adds the radicals to a sulfenamide reagent to produce sulfenamides. Based on the above research, the present invention attempts to use alkyl alcohols as starting materials and sulfenyl imines as reactants. In the early stages of the present invention, organic and inorganic photocatalysts are added to participate in the reaction. In the exploration of reaction conditions, it is found that not using a photocatalyst has no effect on the reaction.

[0005] The present invention proposes a new technology for synthesizing sulfenamide compounds by light-driven reaction without catalyst using alkyl alcohol and sulfenyl imine as reactants. In the technology, the reactant alcohol is a bulk chemical with a wide range of sources and is easily available; at the same time, the other raw material sulfenyl imine is easy to prepare and has good stability and is not easy to decompose, and is an ideal sulfenamide reagent; finally, the reaction in the present invention only needs visible light to drive, without any external photocatalyst, making the whole process more green and efficient. Summary of the invention

[0006] The present invention provides a new method for synthesizing a sulfenamide compound, wherein an alkyl alcohol is converted into an alkyl xanthate in situ in a one-pot method, and then reacted with a trivalent phosphine compound and a sulfenyl imine under light conditions to generate a sulfenamide. The present invention has the advantages of mild reaction conditions, convenient experimental operation, good substrate compatibility, and easy scale-up, laying a solid foundation for further industrial application and creation of social and economic value.

[0007] The technical solution of the present invention:

[0008] A method for synthesizing sulfenamide compounds without catalysts and driven by light, wherein alkyl alcohol (1), potassium tert-butoxide and carbon disulfide are used as starting materials to generate alkyl xanthate (1') in situ by a one-pot method, and then react with a trivalent phosphine compound and sulfenyl imine (2) under light conditions to prepare a series of sulfenamide compounds (3). The synthesis route is as follows:

[0009]

[0010] In the formula: R is selected from one of alkanes, alkenes, aromatic groups and heterocycles, and the alkyl alcohol is selected from primary alcohols, secondary alcohols and tertiary alcohols;

[0011] Here are the steps:

[0012] (1) Using alkyl alcohol (1) and potassium tert-butoxide as starting materials, THF as solvent, the molar ratio of alkyl alcohol, potassium tert-butoxide and CS2 is 1:1.2:3, and the reaction concentration is 0.1 mol / L. Stirring at room temperature for 30-60 minutes, then adding CS2 and reacting at 0°C for 2-3 hours, alkyl xanthate (1') is generated in situ by a one-pot method;

[0013] (2) Under light conditions, alkyl xanthate (1') reacts with a trivalent phosphine compound and sulfenyl imide (2) in a solvent to prepare a series of sulfenamide compounds (3);

[0014] The trivalent phosphine compound is selected from tricyclohexylphosphine, dicyclohexylphenylphosphine, DPPE, tri-tert-butylphosphine, triphenylphosphine, 1,3-bis(dicyclohexylphosphino)butane and n-butyldi(1-adamantyl)phosphine.

[0015] The wavelength range is 390nm~456nm.

[0016] The light reaction time ranges from 8 to 24 hours, preferably from 12 to 18 hours.

[0017] The solvent is selected from one or a mixture of two or more of toluene, n-hexane, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, dichloromethane, acetone, acetonitrile, ethanol, and methanol, preferably ethanol, acetonitrile, and acetone.

[0018] The concentration of the alkyl xanthate in the organic solvent is 0.075 mmol / mL to 0.3 mmol / mL.

[0019] The molar ratio of the alkyl xanthate to the sulfenyl imide is 1:1 to 1:2.

[0020] The molar ratio of the alkyl xanthate to the trivalent phosphine compound is 1:1 to 1:2.

[0021] Beneficial effects of the present invention: The present invention is a new method for preparing sulfenamide, which realizes the light-driven deoxygenation coupling reaction of alkyl alcohol and sulfenimine under the condition of no photocatalyst for the first time, filling the existing technical gap. The method of the present invention has mild process conditions, short process, simple steps, wide application range of substrates, easy scale-up, and a yield of up to 82%, which can meet the needs of industrial production. On the other hand, the sulfenamide generated by the reaction has broad application prospects in organic synthesis and drug research and development. In summary, the present invention has important application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 For compound 3a 1 H-NMR spectrum.

[0023] Figure 2 For compound 3a 13 C-NMR spectrum.

[0024] Figure 3 For compound 3b 1 H-NMR spectrum.

[0025] Figure 4 For compound 3b 13 C-NMR spectrum.

[0026] Figure 5 For compound 3c 1 H-NMR spectrum.

[0027] Figure 6 For compound 3c 13 C-NMR spectrum.

[0028] Figure 7 For compound 3d 1 H-NMR spectrum.

[0029] Figure 8 For compound 3d 13 C-NMR spectrum.

[0030] Fig. 9 For compound 3e 1 H-NMR spectrum.

[0031] Fig.10 For compound 3e 13 C-NMR spectrum.

[0032] Fig.11 For compound 3f 1 H-NMR spectrum.

[0033] Fig.12 For compound 3f 13 C-NMR spectrum.

[0034] Fig.13 For compound 3g 1 H-NMR spectrum.

[0035] Fig.14 For compound 3g 13 C-NMR spectrum.

[0036] Fig.15 For compound 3g 19 F-NMR spectrum.

[0037] Fig.16 For compound 3h 1 H-NMR spectrum.

[0038] Fig.17 For compound 3h 13 C-NMR spectrum.

[0039] Fig.18 For compound 3i 1 H-NMR spectrum.

[0040] Fig.19 For compound 3i 13 C-NMR spectrum.

[0041] Fig. 20 For compound 3j 1 H-NMR spectrum.

[0042] Fig.21 For compound 3j 13 C-NMR spectrum.

[0043] Fig. 22 For compound 3k 1 H-NMR spectrum.

[0044] Fig.23 For compound 3k 13 C-NMR spectrum. DETAILED DESCRIPTION

[0045] The specific implementation of the present invention is further described below in conjunction with the accompanying drawings and technical solutions.

[0046] Example 1: Synthesis of 2-phenyl-N-tritylethane-1-sulfinamide (3a)

[0047]

[0048] In the glove box, phenylethanol (36.7 mg, 0.3 mmol) and KO tBu (40.4 mg, 0.36 mmol) and dry THF (3.0 mL) were stirred at room temperature for 30 minutes, and then CS2 (54.1 μL, 0.9 mmol) was added at 0 degrees to react for 3 hours. After the reaction, the solvent was distilled off under reduced pressure to obtain xanthate, and then sulfenyl imide, n-butyl di(1-adamantyl) phosphine and acetonitrile (3 mL) were added in sequence. The resulting mixture was stirred at room temperature under the irradiation of a blue LED lamp (456 nm) for 16 hours. After the reaction, it was filtered with diatomaceous earth, dried with a vacuum pump, and then separated on a silica gel column using petroleum ether / ethyl acetate as an eluent. The yield of the product 3a was 82%.

[0049] 1 H NMR (400MHz, CDCl3) δ7.30-7.24(m,17H),7.22-7.20(m,1H),7.16-7.14(m,2H),4.89(s,1H),3.06-2.91(m,4H). 13 C NMR (101 MHz, CDCl3) δ 144.74, 139.02, 129.11, 128.68, 128.49, 128.00, 127.33, 126.58, 72.83, 58.25, 29.14. This product is a known compound.

[0050] Example 2: Synthesis of 3-(4-methoxyphenyl)-N-tritylpropane-1-sulfinamide (3b)

[0051]

[0052] In the glove box, weigh 3-(4-methoxyphenyl)-1-propanol (49.9 mg, 0.3 mmol), KO t Bu (40.4 mg, 0.36 mmol) and dry THF (3.0 mL) were stirred at room temperature for 30 minutes, and then CS2 (54.1 μL, 0.9 mmol) was added at 0 degrees to react for 3 hours. After the reaction, the solvent was distilled off under reduced pressure to obtain xanthate, and then sulfenyl imide, tricyclohexylphosphine and acetonitrile (5 mL) were added in sequence. The resulting mixture was stirred at room temperature under the irradiation of a blue LED lamp (440 nm) for 14 hours. After the reaction, it was filtered with diatomaceous earth, dried with a vacuum pump, and then separated on a silica gel column using petroleum ether / ethyl acetate as an eluent. The yield of the product 3b was 65%.

[0053] 1H NMR(400MHz, CDCl3)δ7.26-7.16(m,15H),6.95(d,J=8.6Hz,2H),6.74(d,J=8.6Hz,2H), 4.82(s,1H),3.70(s,3H),2.63(t,J=7.5Hz,2H),2.57-2.49(m,2H),1.91-1.84(m,2H). 13 C NMR (101MHz, CDCl3) δ157.96,144.78,132.53,129.32,129.15,127.94,127.30,113.85,72.84,56.61,55.19,33.45,25.06.HRMS m / z(ESI)calcd for C 29 H 29 NO2S(MH) + 454.1840, found 454.1847.

[0054] Example 3: Synthesis of (E)-3-phenyl-N-tritylprop-2-ene-1-sulfinamide (3c)

[0055]

[0056] In the glove box, cinnamyl alcohol (40.3 mg, 0.3 mmol) and KO t Bu (40.4 mg, 0.36 mmol) and dry THF (3.0 mL) were stirred at room temperature for 30 minutes, and then CS2 (54.1 μL, 0.9 mmol) was added at 0 degrees to react for 3 hours. After the reaction, the solvent was distilled off under reduced pressure to obtain xanthate, and then sulfenyl imide, dicyclohexylphenylphosphine and ethanol (3 mL) were added in sequence. The resulting mixture was stirred at room temperature under the irradiation of a blue LED lamp (456 nm) for 12 hours. After the reaction, it was filtered with diatomaceous earth, dried with a vacuum pump, and then separated on a silica gel column using petroleum ether / ethyl acetate as an eluent. The yield of the product 3c was 56%.

[0057] 1 H NMR (400MHz, CDCl3) δ7.39-7.24(m,20H),6.56(d,J=15.9Hz,1H),6.38-6.31(m,1H),5.11(s,1H),3.72-3.67(m,1H),3.33-3.27(m,1H). 13 C NMR (101MHz,CDCl3) 13C NMR(101MHz,Chloroform-d)δ144.85,138.57,135.97,129.03,128.65,128.26,128.05,127.34,126.56,116.54,72.68,59.84.HRMS m / z(ESI)calcd for C 28 H 25 NOS(M+Na) + 446.1557, found 446.1555.

[0058] Example 4: Synthesis of 2-(4-bromophenyl)-N-tritylethane-1-sulfinamide (3d)

[0059]

[0060] In the glove box, p-bromophenethyl alcohol (60.3 mg, 0.3 mmol) and KO t Bu (40.4 mg, 0.36 mmol) and ultra-dry THF (3.0 mL) were stirred at room temperature for 30 minutes, and then CS2 (54.1 μL, 0.9 mmol) was added at 0 degrees to react for 3 hours. After the reaction, the solvent was distilled off under reduced pressure to obtain xanthate, and then sulfenyl imide, tert-butyl dicyclohexyl phosphine and acetone (3 mL) were added in sequence. The resulting mixture was stirred at room temperature under the irradiation of a blue LED lamp (456 nm) for 16 hours. After the reaction, it was filtered with diatomaceous earth, dried with a vacuum pump, and then separated on a silica gel column using petroleum ether / ethyl acetate as an eluent. The yield of the product 3d was 60%.

[0061] 1 H NMR (400MHz, CDCl3) δ7.38 (d, J = 8.4Hz, 2H), 7.32-7.25 (m, 15H), 7.01 (d, J = 8.4Hz, 2H), 4.86 (s, 1H), 3.00-2.85 (m, 4H). 13 C NMR(101MHz, CDCl3)δ144.68,137.96,131.74,130.24,129.06,128.04,127.39,120.44,72.88,58.03,28.68.HRMS m / z(ESI)calcd for C 27 H 24 BrNOS(M+Cl) - 526.0436,found526.0424.

[0062] Example 5: Synthesis of Tert-butyl(4-(2-((tritylamino)sulfinyl)ethyl)phenyl)carbamate(3e)

[0063]

[0064] In the glove box, weigh N-Boc-2-(4-aminophenyl)ethanol (71.2 mg, 0.3 mmol), KO t Bu (40.4 mg, 0.36 mmol) and ultra-dry THF (3.0 mL) were stirred at room temperature for 30 minutes, and then CS2 (54.1 μL, 0.9 mmol) was added at 0 degrees to react for 3 hours. After the reaction, the solvent was distilled off under reduced pressure to obtain xanthate, and then sulfenyl imide, n-butyl di(1-adamantyl) phosphine and acetonitrile (3 mL) were added in sequence. The resulting mixture was stirred at room temperature under the irradiation of a blue LED lamp (440 nm) for 16 hours. After the reaction, it was filtered with diatomaceous earth, dried with a vacuum pump, and then separated on a silica gel column using petroleum ether / ethyl acetate as an eluent. The yield of the product 3e was 65%.

[0065] 1 H NMR (400MHz, CDCl3) δ7.27-7.22(m,17H),7.03(d,J=7.9Hz,2H),6.48(s,1H),4.84(s,1H),2.96-2.83(m,4H),1.48(s,9H). 13 C NMR(101MHz, CDCl3)δ144.75,136.93,133.49,129.08,129.01,128.02,127.33,118.82,72.80,58.33,28.44,28.32.HRMS m / z(ESI)calcd for C 32 H 34 N2O3S(MH) + 525.2212, found 525.2206.

[0066] Example 6: Synthesis of N-tritylhexane-1-sulfinamide (3f)

[0067]

[0068] In the glove box, weigh n-hexanol (30.7 mg, 0.3 mmol), KO tBu (40.4 mg, 0.36 mmol) and ultra-dry THF (3.0 mL) were stirred at room temperature for 30 minutes, and then CS2 (54.1 μL, 0.9 mmol) was added at 0 degrees to react for 3 hours. After the reaction, the solvent was distilled off under reduced pressure to obtain xanthate, and then sulfenyl imide, n-butyl di(1-adamantyl) phosphine and acetone (3 mL) were added in sequence. The resulting mixture was stirred at room temperature under the irradiation of a blue LED lamp (456 nm) for 10 hours. After the reaction, it was filtered with diatomaceous earth, dried with a vacuum pump, and then separated on a silica gel column using petroleum ether / ethyl acetate as an eluent. The yield of the product 3f was 84%.

[0069] 1 H NMR (400MHz, CDCl3) δ7.29-7.14(m,15H),4.86(s,1H),2.62-2.55(m,2H),1.57-1.49(m,2H),1.25-1.11(m,6H),0.77(t,J=6.7Hz,3H). 13 C NMR(101MHz, CDCl3)δ144.84,129.12,127.87,127.20,72.73,57.52,31.23,28.14,23.16,22.26,13.87.HRMS m / z(ESI)calcd for C 25 H 29 NOS(MH) + 390.1892, found 390.1887.

[0070] Example 7: Synthesis of 2-chloro-1-phenoxyallyl pivalate (3 g)

[0071]

[0072] In the glove box, weigh 4,4,4-trifluorobutanol (38.4 mg, 0.3 mmol), KO t Bu (40.4 mg, 0.36 mmol) and ultra-dry THF (3.0 mL) were stirred at room temperature for 30 minutes, and then CS2 (54.1 μL, 0.9 mmol) was added at 0 degrees to react for 3 hours. After the reaction, the solvent was distilled off under reduced pressure to obtain xanthate, and then sulfenyl imide, n-butyl di(1-adamantyl) phosphine and ethanol (4 mL) were added in sequence. The resulting mixture was stirred at room temperature under the irradiation of a blue LED lamp (456 nm) for 16 hours. After the reaction, it was filtered with diatomaceous earth, dried with a vacuum pump, and then separated on a silica gel column using petroleum ether / ethyl acetate as an eluent. The yield of the product 3 g was 49%.

[0073] 1 H NMR (400MHz, CDCl3) δ7.32-7.25(m,15H),5.01(s,1H),2.79-2.68(m,2H),2.17-2.05(m,2H),1.90(q,J=7.5Hz,2H). 13 C NMR (101MHz, CDCl3) δ144.63,129.11,128.05,127.45,72.96,55.80,32.60,32.31,16.67,16.64. 19 F NMR(377MHz, CDCl3)δ-66.11,-66.13,-66.16.HRMS m / z(ESI)calcd for C 23 H 22 F3NOS(MH) + 416.1296, found 416.1310.

[0074] Example 8: Synthesis of N-trityltetrahydro-2H-pyran-4-sulfinamide (3h)

[0075]

[0076] In the glove box, tetrahydropyran-4-ol (30.6 mg, 0.3 mmol) and KO t Bu (40.4 mg, 0.36 mmol) and ultra-dry THF (3.0 mL) were stirred at room temperature for 30 minutes, and then CS2 (54.1 μL, 0.9 mmol) was added at 0 degrees to react for 3 hours. After the reaction, the solvent was distilled off under reduced pressure to obtain xanthate, and then sulfenyl imide, tricyclohexylphosphine and acetonitrile (3 mL) were added in sequence. The resulting mixture was stirred at room temperature under blue LED light (390 nm) for 12 hours. After the reaction, it was filtered with diatomaceous earth, dried with a vacuum pump, and then separated with a silica gel column using petroleum ether / ethyl acetate as eluent. The yield of the product 3h was 68%.

[0077] 1 H NMR (400MHz, CDCl3) δ7.43–7.19(m,15H),4.80(s,1H),4.03(m,2H),3.39(td,J= 11.6,2.4Hz,2H),2.77(tt,J=11.7,4.1Hz,1H),1.92(m,2H),1.81–1.59(m,2H). 13C NMR(101MHz, CDCl3)δ144.66,129.34,127.92,127.38,73.00,66.95,66.83,61.33,26.58,26.21.HRMS m / z(ESI)calcd for C 24 H 25 NO2S(MH) + 390.1528, found 390.1538.

[0078] Example 9: Synthesis of N-tritylcyclohexanesulfinamide (3i)

[0079]

[0080] Cyclohexanol (30.1 mg, 0.3 mmol), KO t Bu (40.4 mg, 0.36 mmol) and ultra-dry THF (3.0 mL) were stirred at room temperature for 30 minutes, and then CS2 (54.1 μL, 0.9 mmol) was added at 0 degrees to react for 3 hours. After the reaction, the solvent was distilled off under reduced pressure to obtain xanthate, and then sulfenyl imide, n-butyl di(1-adamantyl) phosphine and acetonitrile (5 mL) were added in sequence. The resulting mixture was stirred at room temperature under the irradiation of a blue LED lamp (456 nm) for 12 hours. After the reaction, it was filtered with diatomaceous earth, dried with a vacuum pump, and then separated on a silica gel column using petroleum ether / ethyl acetate as an eluent. The yield of the product 3i was 86%.

[0081] 1 H NMR (400MHz, CDCl3) δ7.56-7.04(m,15H),4.77(s,1H),2.51(tt,J=11.3,3.7Hz,1H),2.09- 1.95(m,2H),1.82(tt,J=16.6,3.8Hz,2H),1.64(dd,J=11.2,5.0Hz,1H),1.50-1.14(m,5H). 13 C NMR (101 MHz, CDCl3) δ 144.88, 129.32, 127.85, 127.23, 72.80, 64.13, 26.67, 25.52, 25.45, 25.36, 25.17. The product is a known compound.

[0082] Example 10: Synthesis of (3s,5s,7s)-N-trityladamantane-1-sulfinamide (3j)

[0083]

[0084] In the glove box, weigh 1-adamantanol (45.7 mg, 0.3 mmol), KO t Bu (40.4 mg, 0.36 mmol) and ultra-dry THF (3.0 mL) were stirred at room temperature for 30 minutes, and then CS2 (54.1 μL, 0.9 mmol) was added at 0 degrees to react for 3 hours. After the reaction, the solvent was distilled off under reduced pressure to obtain xanthate, and then sulfenyl imide, dicyclohexylphenylphosphine and ethanol (3 mL) were added in sequence. The resulting mixture was stirred at room temperature under the irradiation of a blue LED lamp (456 nm) for 16 hours. After the reaction, it was filtered with diatomaceous earth, dried with a vacuum pump, and then separated on a silica gel column using petroleum ether / ethyl acetate as an eluent. The yield of the product 3j was 59%.

[0085] 1 H NMR (400MHz, CDCl3) δ7.36-7.22(m,15H),4.59(s,1H),2.20-2.11(m,3H),1.95-1.87(m,3H),1.85-1.78(m,3H),1.78-1.63(m,6H). 13 C NMR (101 MHz, CDCl3) δ 145.03, 129.55, 127.82, 127.26, 72.65, 58.95, 36.42, 35.21, 28.72. The product is a known compound.

[0086] Example 11: Synthesis of 2-methyl-N-tritylhexane-2-sulfinamide (3k)

[0087]

[0088] In the glove box, weigh 2-methyl-2-hexanol (34.8 mg, 0.3 mmol), KO t Bu (40.4 mg, 0.36 mmol) and ultra-dry THF (3.0 mL) were stirred at room temperature for 30 minutes, and then CS2 (54.1 μL, 0.9 mmol) was added at 0 degrees to react for 3 hours. After the reaction, the solvent was distilled off under reduced pressure to obtain xanthate, and then sulfenyl imine, 1,3-bis(dicyclohexylphosphino)butane and acetonitrile (3 mL) were added in sequence. The resulting mixture was stirred at room temperature under the irradiation of a blue LED lamp (456 nm) for 18 hours. After the reaction, it was filtered with diatomaceous earth, dried with a vacuum pump, and then separated on a silica gel column using petroleum ether / ethyl acetate as an eluent. The yield of the product 3k was 58%.

[0089] 1H NMR (400MHz, CDCl3) δ7.37-7.17(m,15H),4.52(s,1H),1.69-1.57(m,1H),1. 53-1.38(m,1H),1.35-1.23(m,4H),1.20(d,J=7.0Hz,6H),0.91-0.83(m,3H). 13 C NMR(101MHz, CDCl3)δ144.94,129.58,127.79,127.29,72.87,60.34,36.09,25.70,23.25,20.09,19.95,13.91.HRMS m / z(ESI)calcd for C 26 H 31 NOS(MH) + 404.2048, found 404.2043.

[0090] Example 12: Synthesis of 2-phenyl-N-tritylethane-1-sulfinamide (3a) (with photocatalyst)

[0091]

[0092] In the glove box, phenylethanol (36.7 mg, 0.3 mmol) and KO t Bu (40.4 mg, 0.36 mmol) and dry THF (3.0 mL) were stirred at room temperature for 30 minutes, and then CS2 (54.1 μL, 0.9 mmol) was added at 0 degrees to react for 3 hours. After the reaction, the solvent was distilled off under reduced pressure to obtain xanthate, and then sulfenyl imide, n-butyl di(1-adamantyl)phosphine, 4CzIPN and acetonitrile (3 mL) were added in sequence. The resulting mixture was stirred at room temperature under blue LED light (456 nm) for 16 hours. After the reaction, it was filtered with diatomaceous earth, dried with a vacuum pump, and then separated with petroleum ether / ethyl acetate as eluent on a silica gel column. The yield of product 3a was 83%. The experimental results using photocatalysts did not show a significant increase in yield compared with the results without photocatalysts, so this reaction does not require photocatalysts.

Claims

1. A method for synthesizing sulfenamide compounds by light-driven synthesis without catalyst, characterized in that: Alkyl xanthate (1') is generated in situ using alkyl alcohol (1), potassium tert-butoxide and carbon disulfide as starting materials through a one-pot method, and then reacts with a trivalent phosphine compound and sulfenyl imide (2) under light conditions to prepare a series of sulfenamide compounds (3). The synthetic route is as follows: Wherein: R is selected from one of alkanes, alkenes, aryls and heterocycles; Here are the steps: (1) Using alkyl alcohol and potassium tert-butoxide as starting materials and THF as solvent, stirring at room temperature for 30 to 60 minutes, then adding CS2 and reacting at 0°C for 2 to 3 hours to generate alkyl xanthate in situ through a one-pot method; The molar ratio of alkyl alcohol, potassium tert-butoxide and CS2 is 1:1.2:3, and the reaction concentration is 0.1 mol / L; (2) Under light conditions, alkyl xanthate, trivalent phosphine compound and sulfenyl imide react in a solvent to prepare a series of sulfenamide compounds; Wherein, the concentration of alkyl xanthate in the solvent is 0.075 mmol / mL to 0.3 mmol / mL; The molar ratio of alkyl xanthate to sulfenyl imide is 1:1 to 1:2; The molar ratio of the added amount of the alkyl xanthate to the trivalent phosphine compound is 1:1 to 1:

2.

2. The method according to claim 1, characterized in that The alkyl alcohol is selected from the group consisting of primary alcohols, secondary alcohols and tertiary alcohols.

3. The method according to claim 1, characterized in that The trivalent phosphine compound is selected from tricyclohexylphosphine, dicyclohexylphenylphosphine, DPPE, tri-tert-butylphosphine, triphenylphosphine, 1,3-bis(dicyclohexylphosphino)butane and n-butyldi(1-adamantyl)phosphine.

4. The method according to claim 1, characterized in that: The solvent is one or a mixture of two or more of toluene, n-hexane, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, dichloromethane, acetone, acetonitrile, ethanol and methanol.

5. The method according to claim 1, characterized in that The wavelength range of the light is 390nm~456nm.

6. The method according to claim 1, characterized in that The light reaction time is 8 to 24 hours.

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