A method for synthesizing diphenyl sulfide compounds based on heterogeneous catalysts

Abstract

A preparation method of a diphenyl sulfide compound based on a heterogeneous catalyst. The invention relates to a synthesis method of a compound. The invention adds a phenyl halide, a sulfur source, a catalyst and a base to an organic solvent, controls the temperature between room temperature and 100°C, and reacts for 8 to 32 hours under magnetic stirring conditions; after the reaction, the reaction liquid is cooled to room temperature, the solid catalyst is filtered, water and ethyl acetate are added to the liquid reaction mixture, the reaction product is extracted with ethyl acetate, and the solvent is evaporated to obtain a diphenyl sulfide compound; or the product is further purified by a chromatography column; the reaction substrate is a phenyl halide. The method has low catalyst synthesis cost, mild reaction conditions, simple reaction process, and easy separation of the catalyst and the reaction product.

Description

Technical Field

[0001] The invention relates to a method for synthesizing a compound, in particular to a method for synthesizing a diphenyl sulfide compound based on a heterogeneous catalyst. Background Art

[0002] Due to its wide application in organic synthesis, medicinal chemistry and material synthesis, the formation of carbon-sulfur bonds is one of the most important chemical reactions, among which the cross-linking reaction of aryl halides with thiols is the most common synthetic method for C-S bond formation. However, the main limitation of this method is the use of volatile and unpleasant odor thiols, which leads to inevitable environmental and safety issues. At the same time, since thiols tend to bind to transition metals, they are prone to deactivating transition metal catalysts. In addition, the reaction requires harsh reaction conditions, so this method is not suitable for compounds containing sensitive functional groups.

[0003] In order to overcome these shortcomings, in recent years, researchers have developed different transition metal catalysts such as Ni, Fe, Pd, Cu, and Co to prepare aromatic sulfides with various sulfur sources other than mercaptans and aromatic halides. Although these studies have made significant progress in improving the above problems, such as using various sulfur substitutes such as thioacetamide, thiourea, potassium thiocyanate, potassium thioacetate, potassium xanthate, carbon disulfide, and elemental sulfur to replace mercaptans, and although these discoveries have achieved breakthroughs in the field of mercaptan-free CS bond formation, such studies still have some problems, such as the use of organic ligands containing N and P as catalysts, high reaction temperatures, long reaction times, and the use of highly volatile, harmful, and toxic organic solvents. Summary of the invention

[0004] The object of the present invention is to provide a method for synthesizing diphenyl sulfide compounds based on a heterogeneous catalyst. The present invention uses a cheap Ni-based composite metal oxide as a catalyst to prepare diphenyl sulfide under mild conditions. The catalyst of the method is cheap, easily available and easy to recycle and reuse, and a higher diphenyl sulfide yield can be obtained under relatively mild reaction conditions.

[0005] The objective of the present invention is achieved through the following technical solutions:

[0006] The technical solution adopted by the present invention is:

[0007] A method for synthesizing a diphenyl sulfide compound based on a heterogeneous catalyst: adding a phenyl halide, a sulfur source, a composite metal oxide catalyst and a base to an organic solvent, controlling the temperature between room temperature and 100°C, and reacting for 8 to 32 hours under magnetic stirring conditions. After the reaction is completed, the reaction solution is cooled to room temperature, the catalyst is filtered to remove, water and ethyl acetate are added to the reaction mixture, the reaction product is extracted with ethyl acetate, and the solvent is evaporated to obtain a diphenyl sulfide compound. The product can be further purified by a chromatography column. The catalyst can be reused after being washed with ethanol and dried, and the ethyl acetate and water in the reaction solution are evaporated and dried with anhydrous sodium sulfate before being recycled.

[0008] The above-mentioned method for synthesizing diphenyl sulfide compounds based on a heterogeneous catalyst, wherein the catalyst is a heterogeneous nickel-based composite metal oxide Ni y M z O x , wherein M is a cheap transition metal other than Ni, such as Cu, Fe, Ce, Zr, Mn, Co, Cr, etc., preferably Cu, Fe and Co.

[0009] The above-mentioned method for synthesizing diphenyl sulfide compounds based on a heterogeneous catalyst, wherein the catalyst is a heterogeneous nickel-based composite metal oxide Ni y M z O x , y and z are the ratio of the simplest atomic numbers of Ni and M, y:z=1:10 to 10:1, preferably 1:1 to 3:1.

[0010] In the above-mentioned method for synthesizing diphenyl sulfide compounds based on heterogeneous catalysts, the reaction substrate is a phenyl halide, and its structure is shown in formula (I). Wherein X is F, Cl, Br and I, and R is H, C n H 2n+1 , OC n H 2n+1 、X、CHO、CN、NO 2 , C n H 2n+1 Substituents such as CO and heterocyclic ring. (n=1~8)

[0011]

[0012] In the above-mentioned method for synthesizing diphenyl sulfide compounds based on heterogeneous catalysts, the organic solvent is a polar solvent such as DMSO, DMF or DMAc, preferably DMSO.

[0013] In the above-mentioned method for synthesizing diphenyl sulfide compounds based on heterogeneous catalysts, the amount of the catalyst used is expressed as a concentration ranging from 0.002 to 0.1 g‧mL in the reaction system. -1, preferably 0.01~0.05 g‧mL -1 .

[0014] In the above-mentioned method for synthesizing diphenyl sulfide compounds based on heterogeneous catalysts, the sulfur source used in the reaction is one of sulfides such as elemental sulfur, thiourea, and thiocyanate, and the preferred sulfur source is elemental sulfur or thiourea.

[0015] In the above-mentioned method for synthesizing diphenyl sulfide compounds based on heterogeneous catalysts, the amount of the sulfur source is 0.4 to 0.6 times the amount of the reactant phenyl halide substance, and the preferred amount of the sulfur source is 0.5 times the amount of the reactant phenyl halide substance.

[0016] The above-mentioned method for synthesizing diphenyl sulfide compounds based on heterogeneous catalysts, wherein the base is one of inorganic bases such as lithium carbonate, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium hydroxide, rubidium carbonate, cesium carbonate, tert-butyl potassium, tert-butyl sodium, sodium acetate and sodium ethoxide, and the preferred base is sodium carbonate, potassium carbonate, potassium hydroxide and sodium ethoxide.

[0017] In the above-mentioned method for synthesizing diphenyl sulfide compounds based on heterogeneous catalysts, the amount of the base substance is 1 to 5 times that of the reaction substrate phenyl halide, and preferably the amount of the base substance is 1 to 3 times that of the reaction substrate phenyl halide.

[0018] In the above-mentioned method for synthesizing diphenyl sulfide compounds based on heterogeneous catalysts, the reaction temperature is room temperature to 100°C, and the preferred reaction temperature is 60 to 80°C.

[0019] In the above-mentioned method for synthesizing diphenyl sulfide compounds based on heterogeneous catalysts, the reaction time is 8 to 32 h, and the preferred reaction time is 16 to 24 h.

[0020] The beneficial effects of the present invention are:

[0021] The present invention is the first to use a Ni-based composite metal oxide catalyst for the reaction of preparing diphenyl sulfide, which has low catalyst cost, good selectivity and mild reaction conditions; (2) Through the method of the present invention, a phenyl halide and a sulfur source are cross-coupled to prepare a diphenyl sulfide compound, and the yield of the diphenyl sulfide compound is more than 85%; (3) The catalyst and product separation process is simple, and the in-situ catalyst is easy to reuse and can be recycled for more than 10 times, which effectively reduces the catalyst preparation cost; (4) The heterogeneous phase, sulfur source and organic solvent used in the present invention are chemically stable and do not pollute the environment. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The catalyst Ni of the present invention 2 Cu 1 Ox Cycle usage status diagram. DETAILED DESCRIPTION

[0023] The present invention will be further described in detail below by way of examples, but the examples are not intended to limit the present invention.

[0024] Example 1 Catalyst Ni 2 Cu 1 O x Preparation

[0025] Accurately weigh 14.54 g Ni(NO 3 ) 2 ‧6H 2 O (0.05 mol) and 8.40 g NH 3 HCO 3 (0.1 mol) was dissolved in 200 mL of deionized water and 100 mL of anhydrous ethanol. The mixture was transferred to an oil bath at 60 °C and stirred for 3 h to obtain a light green mixed solution. After the temperature dropped to 25 °C, it was filtered, washed, and separated. Finally, it was transferred to a muffle furnace and the calcination temperature was set at 400 °C for 3 h to successfully obtain NiO powder.

[0026] 1.88 g Cu(NO 3 ) 2 To 50 mL of HO 2 O and mix well. Weigh 1.55 g NiO powder and dissolve it in 50 mL50 g·L -1 In PEG solution, ultrasonic dispersion was performed for 30 min, and Cu(NO 3 ) 2 The solution was directly mixed with the NiO solution after ultrasonic treatment, and heated in an oil bath pot. The oil bath temperature was set to 60 °C. The reaction was terminated after 6 h. When the temperature dropped to room temperature, the product was filtered, washed, separated and dried, and then transferred to a muffle furnace at 300 °C for calcination for 3 h to obtain Ni 2 Cu 1 O x Composite oxides.

[0027] Example 2 Ni 2 Cu 1 O x Catalytic reaction of iodobenzene with elemental sulfur to prepare diphenyl sulfide compounds

[0028] The structural formula of diphenyl sulfide prepared by the reaction of iodobenzene and elemental sulfur is shown below:

[0029]

[0030] Add iodobenzene (1 mmol), S 8 (0.5 mmol), Ni 2 Cu 1 O x (0.3 g, 0.02 g‧mL -1 ), KOH (3 mmol) and DMSO (15 mL), react at 60 °C for 24 h. After the reaction, filter out the solid catalyst, add 15 mL of distilled water to the reaction mixture, and then extract with ethyl acetate (30 mL × 2). Evaporate the ethyl acetate phase solution to obtain a crude product, which was purified by column chromatography to obtain the target product with a yield of 91%. Evaporate the water in the lower layer solution and use anhydrous Na 2 SO 4 It can be recycled after drying.

[0031] NMR data: 1 H NMR (CDCl 3 , 400MHz) d (ppm):7.34-7.30 (m, 4H), 7.30-7.25(m, 4H), 7.24-7.19(m, 2H). 13 C NMR (CDCl 3 , 125MHz) d (ppm): 135.58, 130.89,129.11, 127.11.

[0032] Example 3 Ni 2 Cu 1 O x Catalytic reaction of 4-methyliodobenzene with elemental sulfur to prepare diphenyl sulfide compounds

[0033] The structural formula of diphenyl sulfide compound prepared by the reaction of 4-methyl iodobenzene and elemental sulfur is shown below:

[0034]

[0035] Add 4-methyliodobenzene (1 mmol), S 8 (0.5 mmol), Ni 2 Cu 1 O x (0.3 g, 0.02 g‧mL -1), KOH (3 mmol) and DMSO (15 mL), react at 60 ℃ for 24 h. After the reaction, filter out the solid catalyst, add 15 mL of distilled water to the reaction mixture, and then extract with ethyl acetate (30 mL × 2). Evaporate the ethyl acetate phase solution to obtain a crude product, which was purified by column chromatography to obtain the target product with a yield of 90%. Evaporate the water in the lower solution and use anhydrous Na 2 SO 4 It can be recycled after drying.

[0036] NMR data: 1 H NMR (CDCl 3 , 400MHz) d (ppm):7.26 (d, J = 8.2 Hz, 4H), 7.15(d, J = 7.9 Hz, 4H), 2.36 (s, 6H). 13 C NMR (CDCl 3 , 125MHz) d (ppm):136.72,132.45, 130.85, 129.75, 21.00.

[0037] Example 3 Ni 2 Cu 1 O x Catalytic reaction of 4-methoxyiodobenzene with elemental sulfur to prepare diphenyl sulfide compounds

[0038] The structural formula of diphenyl sulfide compound prepared by the reaction of 4-methoxyiodobenzene and elemental sulfur is shown below:

[0039]

[0040] In a 50 mL reaction bottle, add 4-methoxyiodobenzene (1 mmol), S 8 (0.5 mmol), Ni 2 Cu 1 O x (0.3 g, 0.02 g‧mL -1 ), KOH (3 mmol) and DMSO (15 mL), react at 60 °C for 24 h. After the reaction, filter out the solid catalyst, add 15 mL of distilled water to the reaction mixture, and then extract with ethyl acetate (30 mL × 2). Evaporate the ethyl acetate phase solution to obtain a crude product, which was purified by column chromatography to obtain the target product with a yield of 89%. Evaporate the water in the lower layer solution and use anhydrous Na 2 SO 4It can be recycled after drying.

[0041] NMR data: 1 H NMR (CDCl 3 , 400MHz) d (ppm):7.32-7.30 (m, 1H), 7.31 - 7.29(m, 3H), 7.27 - 7.25 (m, 3H), 7.24-7.23 (m, 1H), 1.30 (s, 18H). 13 C NMR (CDCl 3 , 125MHz) d (ppm):150.01, 132.45, 130.56, 126.02, 34.36, 31.21.

[0042] Example 4 Ni 2 Cu 1 O x Catalytic reaction of 4-chloroiodobenzene with elemental sulfur to prepare diphenyl sulfide compounds

[0043] The structural formula of diphenyl sulfide compound prepared by the reaction of 4-chloroiodobenzene and elemental sulfur is shown below:

[0044]

[0045] Add 4-chloroiodobenzene (1 mmol), S 8 (0.5 mmol), Ni 2 Cu 1 O x (0.3 g, 0.02 g‧mL -1 ), KOH (3 mmol) and DMSO (15 mL), react at 60 ℃ for 24 h. After the reaction, filter out the solid catalyst, add 15 mL of distilled water to the reaction mixture, and then extract with ethyl acetate (30 mL × 2). Evaporate the ethyl acetate phase solution to obtain a crude product, which was purified by column chromatography to obtain the target product with a yield of 90%. Evaporate the water in the lower solution and use anhydrous Na 2 SO 4 It can be recycled after drying.

[0046] NMR data: 1 H NMR (CDCl 3 , 400MHz) d (ppm):7.42-7.38 (m,4H), 7.37-7.33 13 CNMR (CDCl 3, 125MHz) d (ppm):134.89, 133.91, 133.33, 130.28.

[0047] Example 5 Ni 2 Cu 1 O x Catalytic reaction of 3-chloroiodobenzene with elemental sulfur to prepare diphenyl sulfide compounds

[0048] The structural formula of diphenyl sulfide compound prepared by the reaction of 3-chloroiodobenzene and elemental sulfur is shown below:

[0049]

[0050] Add 3-chloroiodobenzene (1 mmol), S 8 (0.5 mmol), Ni 2 Cu 1 O x (0.3 g, 0.02 g‧mL -1 ), KOH (3 mmol) and DMSO (15 mL), react at 60 °C for 24 h. After the reaction, filter out the solid catalyst, add 15 mL of distilled water to the reaction mixture, and then extract with ethyl acetate (30 mL × 2). Evaporate the ethyl acetate phase solution to obtain a crude product, which was purified by column chromatography to obtain the target product with a yield of 88%. Evaporate the water in the lower layer solution and use anhydrous Na 2 SO 4 It can be recycled after drying.

[0051] NMR data: 1 H NMR (CDCl 3 , 400MHz) d (ppm):7.35 (m,2H), 7.24-7.20. 13 C NMR (CDCl 3 , 125MHz) d (ppm):136.82, 135.19, 130.81, 130.32, 129.12, 127.75.

[0052] Example 6 Ni 2 Cu 1 O x Catalytic reaction of 2-chloroiodobenzene with elemental sulfur to prepare diphenyl sulfide compounds

[0053] The structural formula of diphenyl sulfide compound prepared by the reaction of 2-chloroiodobenzene and elemental sulfur is shown below:

[0054]

[0055] Add 2-chloroiodobenzene (1 mmol), S 8 (0.5 mmol), Ni 2 Cu 1 O x (0.3 g, 0.02 g‧mL -1 ), KOH (3 mmol) and DMSO (15 mL), react at 60 °C for 24 h. After the reaction, filter out the solid catalyst, add 15 mL of distilled water to the reaction mixture, and then extract with ethyl acetate (30 mL × 2). Evaporate the ethyl acetate phase solution to obtain a crude product, which was purified by column chromatography to obtain the target product with a yield of 92%. Evaporate the water in the lower layer solution and use anhydrous Na 2 SO 4 It can be recycled after drying.

[0056] NMR data: 1 H NMR (CDCl 3 , 400MHz) d (ppm):77.43 (dd, J = 7.7, 1.5 Hz, 2H), 7.23-7.12 (m, 6H). 13 C NMR (CDCl 3 , 125MHz) d (ppm):135.51, 133.23, 132.34,130.11, 128.67, 127.53.

[0057] Example 7-12 Reaction of iodobenzene with elemental sulfur to prepare diphenyl sulfide compounds under different conditions

[0058] The structural formula of diphenyl sulfide prepared by the reaction of iodobenzene and elemental sulfur is shown below:

[0059]

[0060] Add iodobenzene (1 mmol), sulfur source, catalyst, base and solvent (15 mL) to a 50 mL reaction bottle and react for a certain time at different temperatures. After the reaction is completed, filter out the solid catalyst, add 15 mL of distilled water to the reaction mixture, and then extract with ethyl acetate (30 mL × 2). Evaporate the ethyl acetate phase solution to obtain a crude product, which is purified by column chromatography to obtain the target product with a yield of 95%. Evaporate the water in the lower layer solution and use anhydrous Na 2 SO 4 After drying, it can be recycled. The experimental results are shown in Table 1.

[0061] Table 1 Optimization of reaction conditions

[0062]

[0063] Example 13 Catalyst Ni 2 Cu 1 O x Recycling

[0064] Take Ni 2 Cu 1 O x As catalyst for the reaction of iodobenzene with S 8 Reaction: Add iodobenzene (1 mmol), S 8 (0.5 mmol), Ni 2 Cu 1 O x (0.3 g, 0.02 g‧mL -1 ), KOH (3 mmol) and DMSO (15 mL), react at 60 °C for 24 h. After the reaction, filter out the solid catalyst, add 15 mL of distilled water to the reaction mixture, and then extract with ethyl acetate (30 mL × 2). Evaporate the ethyl acetate phase solution to obtain a crude product, which is purified by column chromatography to obtain the target product. Evaporate the water in the lower layer solution and purify it with anhydrous Na 2 SO 4 After drying, it can be recycled. Figure 1 As shown, after using it 10 times, a yield of more than 85% can still be obtained.

[0065] Comparative Example 1

[0066] Catalyst-free iodobenzene and S 8 Reaction: Add iodobenzene (1 mmol), S 8 (0.5mmol), KOH (3 mmol) and DMSO (15 mL) were added and reacted at 60 °C for 24 h. After the reaction, the solid catalyst was filtered out, 15 mL of distilled water was added to the reaction mixture, and then extracted with ethyl acetate (30 mL × 2). The ethyl acetate phase solution was evaporated to obtain a crude product, which was purified by column chromatography to obtain the target product. The yield of diphenyl sulfide was 5%.

[0067] Comparative Example 2

[0068] Iodobenzene and S with NiO alone 8 Reaction: Add iodobenzene (1 mmol), S 8(0.5mmol), NiO (0.3 g, 0.02g‧mL -1 ), KOH (3 mmol) and DMSO (15 mL), react at 60 ° C for 24 h. After the reaction, the solid catalyst was filtered out, 15 mL of distilled water was added to the reaction mixture, and then extracted with ethyl acetate (30 mL × 2). The ethyl acetate phase solution was evaporated to obtain a crude product, which was purified by column chromatography to obtain the target product. The yield of diphenyl sulfide was 75%.

[0069] Comparative Example 3

[0070] Iodobenzene and S with only CuO involved 8 Reaction: Add iodobenzene (1 mmol), S 8 (0.5mmol), CuO (0.3 g, 0.02g‧mL -1 ), KOH (3 mmol) and DMSO (15 mL), react at 60 ° C for 24 h. After the reaction, the solid catalyst was filtered out, 15 mL of distilled water was added to the reaction mixture, and then extracted with ethyl acetate (30 mL × 2). The ethyl acetate phase solution was evaporated to obtain a crude product, which was purified by column chromatography to obtain the target product. The yield of diphenyl sulfide was 32%.

[0071] Comparative Example 4

[0072] Fe only 2 O 3 Iodobenzene and S 8 Reaction: Add iodobenzene (1 mmol), S 8 (0.5mmol)、Fe 2 O 3 (0.3 g, 0.02 g‧mL -1 ), KOH (3 mmol) and DMSO (15 mL), react at 60 ℃ for 24 h. After the reaction, the solid catalyst was filtered out, 15 mL of distilled water was added to the reaction mixture, and then extracted with ethyl acetate (30 mL×2). The ethyl acetate phase solution was evaporated to obtain a crude product, which was purified by column chromatography to obtain the target product. The yield of diphenyl sulfide was 15%.

[0073] The above examples show that the present invention can be used to synthesize diphenyl sulfide compounds based on a heterogeneous catalyst. A phenyl halide can be used as a raw material, elemental sulfur or other sulfides can be used as a sulfur source, a highly polar organic solvent can be used as a reaction medium, and a heterogeneous catalyst can be used to react under mild conditions to prepare diphenyl sulfide compounds. The process promotes the synthesis reaction of diphenyl sulfide with a cheap and readily available transition composite metal oxide catalyst, and the two metal oxides promote each other to achieve catalytic activity. The method has low catalyst synthesis cost, mild reaction conditions, simple reaction process, and easy product separation, providing a new process route for the synthesis of diaryl sulfide compounds, which are important pharmaceutical intermediates.

Claims

1. A method for synthesizing a diphenyl sulfide compound based on a heterogeneous catalyst, characterized in that: The method comprises the following steps: (1) Catalyst Ni2Cu1O x Preparation Accurately weigh 14.54 g Ni(NO3)2‧6H2O (0.05 mol) and 8.40 g NH3HCO3 (0.1 mol) and dissolve them in 200 mL deionized water and 100 mL anhydrous ethanol. Transfer the mixture to a 60 °C oil bath and stir for 3 h to obtain a light green mixed solution. When the temperature drops to 25 °C, filter, wash, and separate it. Finally, transfer it to a muffle furnace and set the calcination temperature to 400 °C for 3 h to successfully obtain NiO powder. 1.88 g Cu(NO3)2 was mixed evenly in 50 mL of H2O; 1.55 g NiO powder was weighed and dissolved in 50 mL of 50 g·L-1 PEG solution, and ultrasonic dispersion was performed for 30 min. The Cu(NO3)2 solution was directly mixed with the NiO solution after ultrasonic dispersion, and the mixture was placed in an oil bath and heated at 60 °C. The reaction was terminated after 6 h. When the temperature dropped to room temperature, the product was filtered, washed, separated and dried, and then transferred to a muffle furnace at 300 °C and calcined for 3 h to obtain Ni2Cu1O x Composite oxides; (2) Ni2Cu1O x Catalytic reaction of iodobenzene with elemental sulfur to prepare diphenyl sulfide compounds The structural formula of diphenyl sulfide prepared by the reaction of iodobenzene and elemental sulfur is shown below: ； Add 1 mmol of iodobenzene, 0.5 mmol of S8, 0.3 g, 0.02 g mL -1 Ni2Cu1O x , 3 mmol KOH and 15 mL DMSO, react at 60 ℃ for 24 h; after the reaction, filter out the solid catalyst, add 15 mL distilled water to the reaction mixture, and then extract with 30 mL×2 ethyl acetate; evaporate the ethyl acetate phase solution to obtain a crude product, and use column chromatography to purify the product to obtain the target product with a yield of 91%; evaporate the water in the lower layer solution, dry it with anhydrous Na2SO4 and it can be recycled.

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