Reductive coupling method of aryl sulfide and nitrous oxide

Abstract

The invention relates to a reductive coupling method of aryl sulfide and nitrous oxide, which only needs to use an air bag and a common reaction tube, does not need to use a pressure-resistant tube with potential safety hazards, and takes cobalt bromide (CoBr2) as a catalyst, 4, 7-diphenyl-1, 10-phenanthroline (4, 7-diphe-1, 10-phen) as a ligand, sodium iodide (NaI) as an additive and zinc powder (Zn) as a reducing agent to prepare the aryl sulfide and nitrous oxide reductive coupling method. The method comprises the following steps: under the condition of nitrous oxide of one atmospheric pressure, putting thiazole thioether and derivatives thereof into N, N-dimethylacetamide (DMA), reacting for 12 hours under the condition of 100 DEG C, and then performing column chromatography purification through an automatic column chromatography machine to obtain thiazolone and derivatives thereof. Some important drug molecules can be synthesized by adopting the method.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic compound synthesis, and in particular, relates to a method for the reductive coupling of aryl sulfides and dinitrogen monoxide. Background Art

[0002] Dinitrogen monoxide is a greenhouse gas with a lifespan of 116 years, and its global warming potential is more than 300 times that of carbon dioxide. In the past 150 years, human activities have led to a significant increase in dinitrogen monoxide emissions, resulting in an increase in its atmospheric concentration and further exacerbating environmental problems. As an oxygen transfer reagent, dinitrogen monoxide can act as an oxidant in reactions and simultaneously generate harmless nitrogen by-products. However, due to its weak σ-donor and π-acceptor capabilities, it requires extreme reaction conditions in traditional metal oxide reaction pathways, which limits its application. Recently, the Josep Cornella research group reported a new method for the efficient conversion of aryl halides to phenolic compounds through nickel catalysis under 2 atmospheres of dinitrogen monoxide, which laid the foundation for the nickel-catalyzed conversion of dinitrogen monoxide.

[0003] Compared with nickel, cobalt, as an abundant 3d transition metal, has lower toxicity and exhibits high catalytic activity in reactions such as C-H activation and C-X (X = Cl, Br, I, OTf) bond cleavage. Some studies have shown that cobalt complexes can activate dinitrogen monoxide under atmospheric pressure, but they have not been widely used in the conversion of high-value products. To address this research gap, we expect to develop a method for cobalt-catalyzed C–S bond cleavage under mild conditions using dinitrogen monoxide as an oxygen source. Aryl sulfides, as electrophiles, have the advantages of wide existence and no need for pre-functionalization. We speculate that this research not only provides a new method for the efficient conversion of aryl sulfides but also provides an important direction for the resource utilization of waste. Summary of the Invention

[0004] The object of the present invention is to overcome the deficiencies of the prior art and provide a green and safe method for the reductive coupling of aryl sulfides and dinitrogen monoxide.

[0005] The present invention solves its technical problems by adopting the following technical solutions:

[0006] A method for the reductive coupling of aryl sulfides and dinitrogen monoxide, which includes using aryl sulfides and dinitrogen monoxide as two electrophiles respectively, and successively adding a catalyst, a ligand, an additive, and a reducing agent, adding a solvent, and converting the aryl sulfide into a thiazolone compound under atmospheric pressure. The reaction general formula is:

[0007]

[0008] Wherein, X represents O, S, N;

[0009] R represents an alkyl group or an aryl group.

[0010] Moreover, the ligand is 4,7-diphenyl-1,10-phenanthroline, and its structural formula is:

[0011]

[0012] Moreover, the additive is sodium iodide.

[0013] Moreover, the reducing agent is zinc powder.

[0014] Moreover, the solvent is N,N-dimethylacetamide.

[0015] Moreover, the catalyst is cobalt bromide.

[0016] Moreover, the aryl sulfide is any one of the following compounds:

[0017]

[0018] Among them, R is an independent C1-C 15 alkyl chain or aryl group;

[0019] The alkyl chain includes methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, phenyl;

[0020] R 1 is an independent C1-C 15 alkyl chain, halogen or aryl group;

[0021] The alkyl chain includes methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl;

[0022] The halogen includes fluorine, chlorine, bromine, iodine;

[0023] The aryl group includes phenyl, thiophenyl, methoxyphenyl;

[0024] R 1 is still a carbonyl group, a cyano group, an aldehyde group, a trifluoromethyl group, an alkoxy group, an ester group.

[0025] Moreover, it specifically includes the following steps:

[0026] S1. Add the reactant aryl sulfide compound, catalyst cobalt bromide, ligand 4,7-diphenyl-1,10-phenanthroline, additive NaI, and reducing agent zinc powder into a 10 mL reaction tube in a molar ratio of 1:0.1 - 0.2:0.1 - 0.2:2 - 5:4 - 10. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube, add the solvent N,N-dimethylacetamide to the reaction tube, and stir at 80 - 120 °C for 10 - 15 h;

[0027] S2. Quench the reaction system by adding 1 M HCl solution, extract with ethyl acetate, combine the organic phases and dry with anhydrous Na2SO4. Filter the solution, remove the organic solvent under reduced pressure, and purify by silica gel chromatography to obtain the target product.

[0028] Moreover, the aryl sulfide and nitrous oxide achieve reductive coupling under atmospheric pressure to construct a C - O bond for synthesizing thiazolone compounds.

[0029] The advantages and positive effects of the present invention are:

[0030] 1. The reaction of the present invention avoids operating conditions exceeding one atmosphere, reducing potential safety hazards; the reaction uses phenyl sulfide, a waste in human production and life, as a substrate, making full use of waste resources and being more environmentally friendly; the reaction is carried out by using a low-toxic and inexpensive metal cobalt catalyst, reducing costs and toxicity; the reaction can be used to synthesize a variety of drugs and drug precursors, avoiding the use of highly toxic substrates and improving the safety and applicability of the synthesis.

[0031] 2. The present invention uses cobalt as a catalyst. Compared with nickel, cobalt is an abundant 3d transition metal with lower toxicity. At the same time, in reactions such as C - H activation and C - X (X = Cl, Br, I, OTf) bond cleavage, cobalt exhibits high catalytic activity, which is beneficial to the reaction.

[0032] 3. The aryl sulfide in the present invention exists widely as an electrophilic reagent and does not require pre-functionalization, making the reaction raw materials easy to obtain and reducing the reaction pretreatment steps. There are various types of aryl sulfides in the reactants, and R and R1 can be different alkyl chains, halogens, aryl groups, carbonyl groups, cyano groups, aldehyde groups, trifluoromethyl groups, alkoxy groups, ester groups, etc. This enables the method to prepare a variety of thiazolone compounds with different structures, expanding the diversity and application scope of the products.

[0033] 4. The present invention provides a reductive coupling reaction between aryl sulfides and dinitrogen monoxide under atmospheric pressure, which yields a series of thiazolidinones and their derivatives. This reaction only requires the use of an airbag and a common reaction tube, without the need to use a pressure-resistant tube with potential safety hazards. Some important pharmaceutical molecules can be synthesized by this method. Detailed implementation mode

[0034] The present invention will be further described in detail below through specific examples. The following examples are only descriptive and not restrictive, and the protection scope of the present invention cannot be limited thereby.

[0035] Example 1

[0036]

[0037] A reductive coupling method between aryl sulfides and dinitrogen monoxide includes the following steps:

[0038] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas, and repeat this gas displacement step three times. Then connect a 500 mL dinitrogen monoxide airbag to the reaction tube, and then add 1 mL of the solvent DMA to the reaction tube and stir at 100 °C for 12 hours;

[0039] S2. After the reaction is completed, quench the reaction with 1 M HCl aqueous solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by vacuum distillation, and purify the residue by silica gel column chromatography to obtain a white solid product (80% yield).

[0040] 1 H NMR (500 MHz, DMSO-d6): δ = 9.50 (s, 1H), 7.44–7.38 (m, 1H), 7.29 (dd, J = 7.8, 1.2 Hz, 1H), 7.19–7.12 (m, 2H).

[0041] Example 2

[0042]

[0043] A reductive coupling method between aryl sulfides and dinitrogen monoxide includes the following steps:

[0044] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0045] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvents by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (42% yield).

[0046] 1 1H NMR (500 MHz, DMSO-d6): δ = 9.50 (s, 1H), 7.44–7.38 (m, 1H), 7.29 (dd, J = 7.8, 1.2 Hz, 1H), 7.19–7.12 (m, 2H).

[0047] Example 3

[0048]

[0049] A method for the reductive coupling of aryl sulfide with nitrous oxide, comprising the following steps:

[0050] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0051] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvents by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (55% yield).

[0052] 11H NMR (500 MHz, DMSO-d6): δ = 9.50 (s, 1H), 7.44–7.38 (m, 1H), 7.29 (dd, J = 7.8, 1.2 Hz, 1H), 7.19–7.12 (m, 2H).

[0053] Example 4

[0054]

[0055] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0056] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Then connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA to the reaction tube and stir at 100 °C for 12 hours;

[0057] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by rotary evaporation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (5% yield).

[0058] 1 1H NMR (500 MHz, DMSO-d6): δ = 9.50 (s, 1H), 7.44–7.38 (m, 1H), 7.29 (dd, J = 7.8, 1.2 Hz, 1H), 7.19–7.12 (m, 2H).

[0059] Example 5

[0060]

[0061] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0062] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0063] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by rotary evaporation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (58% yield).

[0064] 1 1H NMR (500 MHz, DMSO-d6): δ = 9.50 (s, 1H), 7.44–7.38 (m, 1H), 7.29 (dd, J = 7.8, 1.2 Hz, 1H), 7.19–7.12 (m, 2H).

[0065] Example 6

[0066]

[0067] A method for the reductive coupling of aryl sulfide with nitrous oxide, comprising the following steps:

[0068] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0069] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by rotary evaporation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (38% yield).

[0070] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.91 (s, 1H), 7.55 (d, J = 8.2 Hz, 1H), 7.11 (dd, J = 8.0, 3.2 Hz, 2H).

[0071] Example 7

[0072]

[0073] A method for the reductive coupling of aryl sulfide and dinitrogen monoxide, comprising the following steps:

[0074] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Then connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0075] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by rotary evaporation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (38% yield).

[0076] 1 H NMR (500 MHz, DMSO-d6): δ = 12.02 (s, 1H), 7.74 (d, J = 2.2 Hz, 1H), 7.31 (dd, J = 8.5, 2.2 Hz, 1H), 7.10 (d, J = 8.5 Hz, 1H).

[0077] Example 8

[0078]

[0079] A method for the reductive coupling of aryl sulfide and dinitrogen monoxide, comprising the following steps:

[0080] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Then connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0081] S2. After the reaction was completed, the reaction was quenched with 1 M aqueous HCl solution, extracted with ethyl acetate, the organic layers were combined, the organic solvent was removed by rotary evaporation under reduced pressure, and the residue was purified by silica gel column chromatography to obtain a white solid product (55% yield).

[0082] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.01 (s, 1H), 7.85 (s, 1H), 7.43 (d, J = 8.5 Hz, 1H), 7.05 (d, J = 8.5 Hz, 1H).

[0083] Example 9

[0084]

[0085] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0086] S1. 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI and 4.0 equivalents of the reducing agent zinc powder were successively added to a 10 mL reaction tube. After evacuating the reaction system through a three-way valve, dinitrogen monoxide gas was introduced, and this gas displacement step was repeated three times. Subsequently, a 500 mL dinitrogen monoxide gas bag was connected to the reaction tube, then 1 mL of the solvent DMA was added to the reaction tube, and the mixture was stirred at 100 °C for 12 hours;

[0087] S2. After the reaction was completed, the reaction was quenched with 1 M aqueous HCl solution, extracted with ethyl acetate, the organic layers were combined, the organic solvent was removed by rotary evaporation under reduced pressure, and the residue was purified by silica gel column chromatography to obtain a white solid product (40% yield).

[0088] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.22 (s, 1H), 8.19 (s, 1H), 7.84 (dt, J = 8.4, 1.8 Hz, 1H), 7.15 (dd, J = 8.3, 1.7 Hz, 1H), 2.45 (s, 3H).

[0089] Example 10

[0090]

[0091] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0092] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0093] S2. After the reaction is completed, quench the reaction with 1 M HCl aqueous solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by rotary evaporation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (37% yield).

[0094] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.29 (s, 1H), 8.22 (d, J = 1.7 Hz, 1H), 7.89 (dd, J = 8.4, 1.8 Hz, 1H), 7.21 (d, J = 8.4 Hz, 1H), 3.84 (s, 3H). 13 13C NMR (126 MHz, DMSO-d6): δ = 170.5, 165.7, 140.4, 128.0, 124.2, 123.9, 123.8, 111.3, 52.1. HRMS (EI) calcd. for C9H7O3NS [M] + : 209.0147, found 209.0137.

[0095] Example 11

[0096]

[0097] A reductive coupling method of aryl sulfide and nitrous oxide, comprising the following steps:

[0098] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0099] S2. After the reaction was completed, the reaction was quenched with 1 M aqueous HCl solution, extracted with ethyl acetate, the organic layers were combined, the organic solvent was removed by vacuum distillation, and the residue was purified by silica gel column chromatography to obtain a white solid product (62% yield).

[0100] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.30 (s, 1H), 8.08 (s, 1H), 7.62 (dd, J = 8.7, 2.3 Hz, 1H), 7.27 (d, J = 8.3 Hz, 1H).

[0101] Example 12

[0102]

[0103] A method for the reductive coupling of aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0104] S1. 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI and 4.0 equivalents of the reducing agent zinc powder were successively added to a 10 mL reaction tube. After evacuating the reaction system through a three-way valve, dinitrogen monoxide gas was introduced. This gas displacement step was repeated three times. Subsequently, a 500 mL dinitrogen monoxide gas bag was connected to the reaction tube, then 1 mL of the solvent DMA was added to the reaction tube, and the mixture was stirred at 100 °C for 12 hours;

[0105] S2. After the reaction was completed, the reaction was quenched with 1 M aqueous HCl solution, extracted with ethyl acetate, the organic layers were combined, the organic solvent was removed by vacuum distillation, and the residue was purified by silica gel column chromatography to obtain a white solid product (53% yield).

[0106] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.42 (s, 1H), 8.14 (d, J = 1.7 Hz, 1H), 7.72 (dd, J = 8.3, 1.7 Hz, 1H), 7.24 (d, J = 8.3 Hz, 1H).

[0107] Example 13

[0108]

[0109] A method for the reductive coupling of aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0110] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% catalyst CoBr2, 12 mol% ligand 4,7-diphen-1,10-phen, 2.0 equivalents of additive NaI, and 4.0 equivalents of reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0111] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvents by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (50% yield).

[0112] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.74 (s, 1H), 7.36 (s, 1H), 7.09–6.98 (m, 2H), 2.29 (s, 3H).

[0113] Example 14

[0114]

[0115] A method for the reductive coupling of aryl sulfide with nitrous oxide, comprising the following steps:

[0116] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% catalyst CoBr2, 12 mol% ligand 4,7-diphen-1,10-phen, 2.0 equivalents of additive NaI, and 4.0 equivalents of reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0117] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvents by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (54% yield).

[0118] 11H NMR (500 MHz, DMSO-d6): δ = 11.75 (s, 1H), 7.44 (d, J = 1.8 Hz, 1H), 7.14 (dd, J = 8.2, 1.8 Hz, 1H), 7.02 (d, J = 8.2 Hz, 1H), 2.88 (p, J = 6.9 Hz, 1H), 1.19 (d, J = 6.9 Hz, 6H). 13 13C NMR (126 MHz, DMSO-d6): 170.1, 143.1, 134.3, 124.7, 123.3, 120.3, 111.3, 33.2, 24.1. HRMS (EI) calcd. for C 10 H 11 ONS [M] + : 193.0561, found 193.0552.

[0119] Example 15

[0120]

[0121] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0122] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Then connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA to the reaction tube and stir at 100 °C for 12 hours;

[0123] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (49% yield).

[0124] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.74 (s, 1H), 7.59 (s, 1H), 7.30 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 8.3 Hz, 1H), 1.27 (s, 12H). 1313C NMR(126MHz,DMSO-d6):δ=170.2,145.4,134.0,123.5,123.1,119.4,111.0,34.4,31.3.HRMS(EI)calcd.for C 11 H 13 ONS[M] + :207.0718,found 207.0708.

[0125] Example 16

[0126]

[0127] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0128] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Then connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0129] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (30% yield).

[0130] 1 1H NMR(500MHz,DMSO-d6):δ=9.41(s,1H),8.49(s,1H),8.16(d,J=8.5Hz,1H),7.85(d,J=8.5Hz,1H),7.77(d,J=7.1Hz,2H),7.51(t,J=7.6Hz,2H),7.40(dd,J=8.3,6.6Hz,1H).

[0131] Example 17

[0132]

[0133] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0134] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0135] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (41% yield).

[0136] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.90 (s, 1H), 7.84 (d, J = 1.9 Hz, 1H), 7.58 (d, J = 8.8 Hz, 2H), 7.52 (dd, J = 8.3, 1.9 Hz, 1H), 7.15 (d, J = 8.3 Hz, 1H), 7.01 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H).

[0137] Example 18

[0138]

[0139] A method for the reductive coupling of aryl sulfide with nitrous oxide, comprising the following steps:

[0140] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0141] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (57% yield).

[0142] 11H NMR (500 MHz, DMSO-d6): δ = 11.96 (s, 1H), 7.92 (s, 1H), 7.55 (d, J = 7.3 Hz, 1H), 7.50 (d, J = 5.0 Hz, 1H), 7.44 (d, J = 3.6 Hz, 1H), 7.15–7.10 (m, 2H). 13 13C NMR (126 MHz, DMSO-d6): 170.0, 142.9, 135.8, 128.7, 128.5, 125.3, 124.4, 124.0, 123.2, 119.6, 111.9. HRMS (EI) calcd. for C11H7ONS2 [M] + : 232.9969, found 232.9960.

[0143] Example 19

[0144]

[0145] A method for the reductive coupling of aryl sulfide and dinitrogen monoxide, comprising the following steps:

[0146] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas replacement step three times. Then connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0147] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (50% yield).

[0148] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.64 (s, 1H), 7.23 (s, 1H), 7.02 (d, J = 7.3 Hz, 1H), 6.88–6.84 (m, 1H), 3.73 (s, 3H).

[0149] Example 20

[0150]

[0151] A method for the reductive coupling of aryl sulfide and dinitrogen monoxide, comprising the following steps:

[0152] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0153] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by rotary evaporation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (59% yield).

[0154] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.03 (s, 1H), 7.61 (dd, J = 8.7, 5.4 Hz, 1H), 7.00 (ddd, J = 9.6, 8.7, 2.6 Hz, 1H), 6.93 (dd, J = 9.3, 2.6 Hz, 1H). 13 13C NMR (126 MHz, DMSO-d6): δ = 170.7, 162.0, 160.1, 137.3, 124.2, 118.7, 109.7, 99.1. 19 19F NMR (471 MHz, DMSO-d6): δ = -114.74. HRMS (EI) calcd for C7H4FNOS [M] + : 198.9998, found 232.9991.

[0155] Example 21

[0156]

[0157] A method for the reductive coupling of aryl sulfide with nitrous oxide, comprising the following steps:

[0158] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0159] S2. After the reaction was completed, the reaction was quenched with 1 M aqueous HCl solution, extracted with ethyl acetate, the organic layers were combined, the organic solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography to obtain a white solid product (75% yield).

[0160] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.03 (s, 1H), 7.61 (dd, J = 8.4, 2.8 Hz, 1H), 7.18 (dd, J = 8.4, 2.2 Hz, 1H), 7.11 (d, J = 2.0 Hz, 1H).

[0161] Example 22

[0162]

[0163] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0164] S1. 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder were successively added to a 10 mL reaction tube. The reaction system was evacuated through a three-way valve and then dinitrogen monoxide gas was introduced. This gas displacement step was repeated three times. Subsequently, a 500 mL dinitrogen monoxide gas bag was connected to the reaction tube, and then 1 mL of the solvent DMA was added to the reaction tube, and the mixture was stirred at 100 °C for 12 hours;

[0165] S2. After the reaction was completed, the reaction was quenched with 1 M aqueous HCl solution, extracted with ethyl acetate, the organic layers were combined, the organic solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography to obtain a white solid product (35% yield).

[0166] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.04 (s, 1H), 7.55 (d, J = 8.3 Hz, 1H), 7.31 (dd, J = 8.3, 2.0 Hz, 1H), 7.24 (d, J = 1.9 Hz, 1H). 13 13C NMR (126 MHz, DMSO-d6): δ = 170.0, 137.7, 125.2, 124.6, 122.8, 118.8, 114.0. HRMS (EI) calcd. for C7H4ONBrS [M] + : 228.9197, found 228.9189.

[0167] Example 23

[0168]

[0169] A method for the reductive coupling of aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0170] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Subsequently, connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0171] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by rotary evaporation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (53% yield).

[0172] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.23 (s, 1H), 7.84 (dd, J = 8.4, 4.1 Hz, 1H), 7.48 (dd, J = 8.9, 3.9 Hz, 1H), 7.33 (d, J = 4.0 Hz, 1H).

[0173] Example 24

[0174]

[0175] A method for the reductive coupling of aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0176] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Subsequently, connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0177] S2. After the reaction was completed, the reaction was quenched with 1 M aqueous HCl solution, extracted with ethyl acetate, the organic layers were combined, the organic solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography to obtain a white solid product (51% yield).

[0178] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.80 (s, 1H), 7.44 (d, J = 8.6 Hz, 1H), 6.82–6.54 (m, 2H), 3.75 (s, 3H).

[0179] Example 25

[0180]

[0181] A method for the reductive coupling of aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0182] S1. 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI and 4.0 equivalents of the reducing agent zinc powder were successively added to a 10 mL reaction tube. The reaction system was evacuated through a three-way valve and then dinitrogen monoxide gas was introduced. This gas displacement step was repeated three times. Subsequently, a 500 mL dinitrogen monoxide gas bag was connected to the reaction tube, and then 1 mL of the solvent DMA was added to the reaction tube, and the mixture was stirred at 100 °C for 12 hours;

[0183] S2. After the reaction was completed, the reaction was quenched with 1 M aqueous HCl solution, extracted with ethyl acetate, the organic layers were combined, the organic solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography to obtain a white solid product (35% yield).

[0184] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.24 (s, 1H), 7.33 (td, J = 8.2, 5.9 Hz, 1H), 7.08–6.99 (m, 2H). 13 13C NMR (126 MHz, DMSO-d6): δ = 169.12, 156.86, 154.93, 138.4, 128.0, 109.9, 109.7, 108.9, 108.7, 108.1, 108.1. 19 19F NMR (471 MHz, DMSO-d6): δ = -115.58. HRMS (EI) calcd. for C7H4ONFS [M] + : 168.9998, found 168.9989.

[0185] Example 26

[0186]

[0187] A method for the reductive coupling of aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0188] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Then connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0189] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by vacuum distillation, and purify the residue by silica gel column chromatography to obtain a white solid product (28% yield).

[0190] 1 H NMR (500 MHz, DMSO-d6): δ = 11.51 (s, 1H), 7.13 (d, J = 8.1 Hz, 1H), 6.98–6.77 (m, 2H), 2.31 (s, 3H). 13 C NMR (126 MHz, DMSO-d6): δ = 154.6, 141.4, 133.2, 130.3, 122.1, 110.1, 109.1, 20.9. HRMS (EI) calcd. for C8H7NO2S [M] + : 181.0197, found 181.0191.

[0191] Example 27

[0192]

[0193] A method for the reductive coupling of aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0194] S1. Add 1.0 equivalent of the reactant aryl thioether compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0195] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (24% yield).

[0196] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.07 (s, 1H), 8.11 (s, 1H), 7.76 (s, 1H), 2.78 (s, 3H). 13 13C NMR (126 MHz, DMSO-d6): δ = 169.9, 166.1, 148.8, 133.6, 133.3, 122.9, 115.0, 104.1, 15.5. HRMS (EI) calcd. for C9H6ON2S3 [M] + : 253.9642, found 253.9632.

[0197] Example 28

[0198]

[0199] A method for the reductive coupling of aryl thioether with nitrous oxide, comprising the following steps:

[0200] S1. Add 1.0 equivalent of the reactant aryl thioether compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0201] S2. After the reaction was completed, the reaction was quenched with 1 M aqueous HCl solution, extracted with ethyl acetate, the organic layers were combined, the organic solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography to obtain a white solid product (40% yield).

[0202] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.08 (s, 1H), 8.23 (dd, J = 4.9, 1.5 Hz, 1H), 7.44 (dd, J = 8.0, 1.5 Hz, 1H), 7.32 (dd, J = 8.0, 4.9 Hz, 1H). 13 13C NMR (126 MHz, DMSO-d6): δ = 167.8, 146.7, 143.8, 132.5, 122.0, 118.1. HRMS (EI) calcd. for C6H4N2OS + : 152.0044, found 152.0039.

[0203] Example 29

[0204]

[0205] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0206] S1. 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% catalyst CoBr2, 12 mol% ligand 4,7-diphen-1,10-phen, 2.0 equivalents of additive NaI, and 4.0 equivalents of reducing agent zinc powder were successively added to a 10 mL reaction tube. The reaction system was evacuated through a three-way valve and then dinitrogen monoxide gas was introduced. This gas displacement step was repeated three times. Subsequently, a 500 mL dinitrogen monoxide gas bag was connected to the reaction tube, then 1 mL of the solvent DMA was added to the reaction tube, and the mixture was stirred at 100 °C for 12 hours;

[0207] S2. After the reaction was completed, the reaction was quenched with 1 M aqueous HCl solution, extracted with ethyl acetate, the organic layers were combined, the organic solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography to obtain a white solid product (68% yield).

[0208] 1 1H NMR (500 MHz, DMSO-d6): δ = 9.84 (s, 1H), 7.23–7.11 (m, 4H).

[0209] Example 30

[0210]

[0211] A method for the reductive coupling of aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0212] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Subsequently, connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0213] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by rotary evaporation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (76% yield).

[0214] 1 1H NMR (500 MHz, DMSO-d6): δ = 9.84 (s, 1H), 7.23–7.11 (m, 4H).

[0215] Example 31

[0216]

[0217] A method for the reductive coupling of aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0218] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Subsequently, connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0219] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by rotary evaporation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (84% yield).

[0220] 11H NMR (500 MHz, DMSO-d6): δ = 11.81 (s, 1H), 7.48 (d, J = 2.0 Hz, 1H), 7.20 (dd, J = 8.3, 2.0 Hz, 1H), 7.09 (d, J = 8.3 Hz, 1H).

[0221] Example 32

[0222]

[0223] A method for the reductive coupling of aryl sulfide and dinitrogen monoxide, comprising the following steps:

[0224] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Then connect a 500 mL dinitrogen monoxide gas bag to the reaction tube. Then add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0225] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (68% yield).

[0226] 1 1H NMR (500 MHz, DMSO-d6): δ = 12.08 (s, 1H), 7.82 (dd, J = 8.2, 1.5 Hz, 1H), 7.77 (d, J = 1.5 Hz, 1H), 7.20 (d, J = 8.2 Hz, 1H), 3.84 (s, 3H).

[0227] Example 33

[0228]

[0229] A method for the reductive coupling of aryl sulfide and dinitrogen monoxide, comprising the following steps:

[0230] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0231] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvents by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (62% yield).

[0232] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.47 (s, 1H), 7.11 (s, 1H), 6.95 (d, J = 0.9 Hz, 2H), 2.31 (s, 3H).

[0233] Example 34

[0234]

[0235] A method for the reductive coupling of aryl sulfide with nitrous oxide, comprising the following steps:

[0236] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0237] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvents by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (79% yield).

[0238] 11H NMR (500 MHz, DMSO-d6): δ = 11.50 (s, 1H), 7.17 (d, J = 8.4 Hz, 1H), 7.09 (dd, J = 8.5, 2.0 Hz, 1H), 7.04 (d, J = 1.9 Hz, 1H), 1.27 (s, 9H). 13 13C NMR (126 MHz, DMSO-d6): δ = 154.8, 146.7, 141.3, 130.1, 118.6, 108.8, 106.7, 34.5, 31.4. HRMS (EI) calcd. for C 11 H 13 O2N[M] + : 191.0946, found 191.0937.

[0239] Example 35

[0240]

[0241] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0242] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas, repeat this gas replacement step three times. Then connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA to the reaction tube, and stir at 100 °C for 12 hours;

[0243] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (79% yield).

[0244] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.81 (s, 1H), 7.58 (s, 1H), 7.32 (d, J = 8.3 Hz, 1H), 7.04 (d, J = 8.3 Hz, 1H).

[0245] Example 36

[0246]

[0247] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0248] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0249] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by rotary evaporation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (76% yield).

[0250] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.83 (s, 1H), 7.30 (dd, J = 8.8, 4.3 Hz, 1H), 7.00 (dd, J = 8.3, 2.7 Hz, 1H), 6.90 (dddd, J = 10.1, 8.8, 2.7, 1.0 Hz, 1H).

[0251] Example 37

[0252]

[0253] A reductive coupling method of aryl sulfide and nitrous oxide, comprising the following steps:

[0254] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0255] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by rotary evaporation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (55% yield).

[0256] 11H NMR (500 MHz, DMSO-d6): δ = 11.84 (s, 1H), 7.29–7.23 (m, 3H). 13 13C NMR (126 MHz, DMSO-d6): δ = 170.0, 137.7, 125.2, 124.6, 122.8, 118.8, 114.0.

[0257] Example 38

[0258]

[0259] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0260] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Then connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0261] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (73% yield).

[0262] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.52 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 6.90–6.85 (m, 2H), 2.31 (s, 3H).

[0263] Example 39

[0264]

[0265] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0266] S1. Add 1.0 equivalent of the reactant aryl thioether compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0267] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvents by vacuum distillation, and purify the residue by silica gel column chromatography to obtain a white solid product (83% yield).

[0268] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.56 (s, 1H), 7.18 (dd, J = 8.8, 1.0 Hz, 1H), 6.65 (dd, J = 2.5, 1.0 Hz, 1H), 6.61 (ddd, J = 8.7, 2.6, 1.0 Hz, 1H), 3.74 (s, 3H).

[0269] Example 40

[0270]

[0271] A method for the reductive coupling of aryl thioether with nitrous oxide, comprising the following steps:

[0272] S1. Add 1.0 equivalent of the reactant aryl thioether compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0273] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvents by vacuum distillation, and purify the residue by silica gel column chromatography to obtain a white solid product (60% yield).

[0274] 11H NMR (500 MHz, DMSO-d6): δ = 11.94 (s, 1H), 7.18–7.12 (m, 2H), 7.06 (dd, J = 6.3, 2.6 Hz, 1H). 13 13C NMR (126 MHz, DMSO-d6): δ = 153.5, 139.6, 131.8, 124.9, 121.9, 113.3, 108.8. HRMS (EI) calcd. for C7H4O2NCl [M] + : 168.9931, found 168.9922.

[0275] Example 41

[0276]

[0277] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0278] S1. Add 1.0 equivalent of the reactant aryl sulfide compound, 10 mol% of the catalyst CoBr2, 12 mol% of the ligand 4,7-diphen-1,10-phen, 2.0 equivalents of the additive NaI, and 4.0 equivalents of the reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce dinitrogen monoxide gas. Repeat this gas displacement step three times. Then connect a 500 mL dinitrogen monoxide gas bag to the reaction tube, and then add 1 mL of the solvent DMA into the reaction tube, and stir at 100 °C for 12 hours;

[0279] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by distillation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (35% yield).

[0280] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.90 (s, 1H), 7.94 (dd, J = 5.2, 1.5 Hz, 1H), 7.48 (dd, J = 7.6, 1.5 Hz, 1H), 7.20 (dd, J = 7.7, 5.2 Hz, 1H).

[0281] Example 42

[0282]

[0283] A method for the reductive coupling of an aryl sulfide with dinitrogen monoxide, comprising the following steps:

[0284] S1. Add 1.0 equivalent of the reactant aryl thioether compound, 10 mol% catalyst CoBr2, 12 mol% ligand 4,7-diphen-1,10-phen, 2.0 equivalents of additive NaI, and 4.0 equivalents of reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0285] S2. After the reaction is completed, quench the reaction with 1 M aqueous HCl solution, extract with ethyl acetate, combine the organic layers, remove the organic solvent by rotary evaporation under reduced pressure, and purify the residue by silica gel column chromatography to obtain a white solid product (77% yield).

[0286] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.80 (s, 1H), 7.61 (s, 1H), 7.42 (s, 1H), 2.74 (s, 3H). 13 13C NMR (126 MHz, DMSO-d6): δ = 163.7, 154.6, 147.9, 140.8, 135.9, 127.4, 99.8, 92.7, 14.3. HRMS (EI) calcd. for C9H6O3N2S [M] + : 222.0099, found 222.0090.

[0287] Example 43

[0288]

[0289] A method for the reductive coupling of aryl thioether with nitrous oxide, comprising the following steps:

[0290] S1. Add 1.0 equivalent of the reactant aryl thioether compound, 10 mol% catalyst CoBr2, 12 mol% ligand 4,7-diphen-1,10-phen, 2.0 equivalents of additive NaI, and 4.0 equivalents of reducing agent zinc powder into a 10 mL reaction tube in sequence. After evacuating the reaction system through a three-way valve, introduce nitrous oxide gas. Repeat this gas displacement step three times. Then connect a 500 mL nitrous oxide gas bag to the reaction tube. Next, add 1 mL of the solvent DMA into the reaction tube and stir at 100 °C for 12 hours;

[0291] S2. After the reaction was completed, the reaction was quenched with 1 M aqueous HCl solution, extracted with ethyl acetate, and the organic layers were combined. The organic solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography to obtain a white solid product (61% yield).

[0292] 1 1H NMR (500 MHz, DMSO-d6): δ = 11.85 (s, 1H), 7.31 (d, J = 8.5 Hz, 1H), 7.17–7.10 (m, 2H).

[0293] Although embodiments of the present invention have been disclosed for illustrative purposes, those skilled in the art will appreciate that: various substitutions, changes and modifications are possible without departing from the spirit and scope of the present invention and the appended claims. Accordingly, the scope of the present invention is not limited to the content disclosed in the embodiments.

Claims

1. A method for the reductive coupling of aryl sulfide and dinitrogen monoxide, characterized in that: It involves using aryl sulfide and nitrous oxide as two electrophilic reagents respectively. A catalyst, a ligand, an additive, and a reducing agent are added in sequence, and then a solvent is added. Under atmospheric pressure, the aryl sulfide is converted into a thiazolone compound, and the reaction general formula is as follows: Among them, X represents O, S, N; R represents an alkyl group or an aryl group.

2. The reductive coupling method of aryl sulfide and dinitrogen monoxide according to claim 1, wherein: The ligand is 4,7-diphenyl-1,10-phenanthroline, and its structural formula is:

3. The reductive coupling method of aryl sulfide and dinitrogen monoxide according to claim 2, characterized in that: The additive is sodium iodide.

4. The method for the reductive coupling of an aryl sulfide with dinitrogen monoxide according to claim 3, wherein: The reducing agent is zinc powder.

5. The method for the reductive coupling of an aryl sulfide and dinitrogen monoxide according to claim 4, wherein: The solvent is N,N-dimethylacetamide.

6. The method for the reductive coupling of an aryl sulfide and dinitrogen monoxide according to claim 5, wherein: The catalyst is cobalt bromide.

7. The method for the reductive coupling of an aryl sulfide with dinitrogen monoxide according to claim 6, characterized in that: The aryl sulfide is any one of the following compounds: wherein, R is an independent C1-C 15 alkyl chain or aryl group; The alkyl chain includes methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, phenyl; R 1 is an independent C1-C 15 alkyl chain, halogen or aryl; The alkyl chain includes methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl; The halogen includes fluorine, chlorine, bromine, iodine; The aryl group includes phenyl, thiophenyl, methoxyphenyl; R 1 It is still a carbonyl group, a cyano group, an aldehyde group, a trifluoromethyl group, an alkoxy group, or an ester group.

8. The method for the reductive coupling of an aryl sulfide with dinitrogen monoxide according to claim 7, characterized in that: Specifically, it includes the following steps: S1. The reactant aryl sulfide compound, the catalyst cobalt bromide, the ligand 4,7-diphenyl-1,10-phenanthroline, the additive NaI, and the reducing agent zinc powder are added to a 10 mL reaction tube in a molar ratio of 1:0.1 - 0.2:0.1 - 0.2:2 - 5:4 - 10 in sequence. The reaction system is evacuated through a three-way valve and then nitrous oxide gas is introduced. This gas replacement step is repeated three times. Subsequently, a 500 mL nitrous oxide gas bag is connected to the reaction tube, the solvent N,N-dimethylacetamide is added to the reaction tube, and the mixture is stirred at 80 - 120 °C for 10 - 15 h; S2. A 1 M HCl solution is added to the reaction system for quenching, extracted with ethyl acetate, the organic phases are combined and dried with anhydrous Na2SO4, the solution is filtered, and the organic solvent is removed under reduced pressure. The target product is obtained through silica gel chromatography purification.

9. The method for the reductive coupling of an aryl sulfide and dinitrogen monoxide according to claim 8, wherein: The aryl sulfide and nitrous oxide achieve reductive coupling under atmospheric pressure to construct a C - O bond to synthesize a thiazolone compound.

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