A method for preparing diphenyl sulfide compounds from aryl sulfonyl chlorides

Abstract

This invention discloses a method for preparing diphenyl sulfide compounds from arylsulfonyl chlorides, comprising the following steps: using a sulfonyl chloride compound as shown in formula (I) as a raw material, adding a catalyst, ligand, additive, base, and solvent to a reactor, and reacting under a nitrogen atmosphere to obtain a diphenyl sulfide compound as shown in formula (II). The reaction equation is as follows: wherein the H on the benzene ring is substituted or not substituted by a substituent R, and when substituted, R is fluorine, chlorine, bromine, methyl, tert-butyl, or trifluoromethyl. This invention provides mild reaction conditions, uses inexpensive and readily available raw materials, and efficiently promotes the preparation of sulfide compounds.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing diphenyl sulfide compounds from aryl sulfonyl chloride. Background Technology

[0002] Sulfur-containing compounds, such as sulfonyl chlorides, thiosulfates, thioethers, thiols, and disulfides, constitute an important class of structures. They are of significant value in the development of pharmaceuticals, pesticides, and functional organic molecules. This has made the construction of CS bonds a major research topic in organic chemistry, leading to the development of several synthetic schemes. Examples include: 1. Cross-coupling between aryl thiols and halide or borate derivatives; 2. CH activation with directing groups. However, these methods all have certain drawbacks. These drawbacks include: the use of expensive iodobenzene or phenylboronic acid analogs, pungent odors, and a limited substrate range.

[0003] Sulfonyl chloride is an inexpensive and readily available sulfur-containing raw material. Due to its odorless and highly reactive properties, sulfonyl chloride is widely used in the synthesis of various sulfur-containing intermediates. In 2001, You's group prepared thioethers using sulfonyl chloride as a raw material, but the substrate was limited to indoleazine (Q.Wu, DBZhao, XRQin, JBLan, JSYou.Chem.Commun., 2011, 47, 9188.). In 2017, Huang's group prepared thioethers using zinc metal reagents, but the instability of organometallic reagents severely limited related applications (Y.Fu, YHSu, QSXu, ZY, Du, YLHu, KHWang, DFHuang, RSC Adv., 2017, 7, 6018.). The sulfonyl chloride-based method developed by Pan's team requires expensive aryl iodides (Y.Wang, F.Zhang, Y.Wang, Y.Pan, Org.Chem.Front., 2017, 4, 31.). Since sulfonyl chloride is an excellent leaving group that can provide a phenyl group under conditions such as heat or light, it is conceivable whether sulfonyl chloride can be used as a raw material for the preparation of thioether compounds. Summary of the Invention

[0004] This invention addresses the shortcomings of existing technologies by providing a clean and efficient method for preparing diphenyl sulfide compounds from arylsulfonyl chlorides.

[0005] The specific technical solution is as follows:

[0006] A method for preparing diphenyl sulfide compounds from aryl sulfonyl chlorides includes the following steps: using a sulfonyl chloride compound as shown in formula (I) as a raw material, adding a catalyst, ligand, additive, base, and solvent to a reactor, and reacting under a nitrogen atmosphere to obtain a diphenyl sulfide compound as shown in formula (II). The reaction equation is as follows:

[0007]

[0008] In this process, the H on the benzene ring is either substituted or not substituted by a substituent R, and when substituted, R is fluorine, chlorine, bromine, methyl, tert-butyl or trifluoromethyl.

[0009] The catalyst is palladium acetate, palladium diacetonitrile chloride, or palladium trifluoroacetate.

[0010] The ligand is 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene, 1,3-bis(diphenylphosphine)propane, or 1,1'-bis(diphenylphosphine)ferrocene.

[0011] The solvent is N,N-dimethylformamide, 1,4-dioxane, or toluene, and the base is potassium fluoride, sodium fluoride, or potassium carbonate.

[0012] The alkali is potassium fluoride, sodium fluoride, or potassium carbonate.

[0013] The additive is cuprous iodide, cuprous bromide, or trimethylsilane.

[0014] Furthermore, the reaction time is 12-15 hours, and the reaction temperature is 130-150℃.

[0015] Furthermore, the molar ratio of the sulfonyl chloride compound shown in formula (Ⅰ) to the catalyst is 3.0–6.0:1.0.

[0016] Furthermore, the molar ratio of the sulfonyl chloride compound to the ligand shown in formula (Ⅰ) is 2.5–4.5:1.0.

[0017] Furthermore, the molar ratio of the sulfonyl chloride compound to the base shown in formula (Ⅰ) is 0.1–1.0:1.0.

[0018] Furthermore, the molar ratio of the sulfonyl chloride compound shown in formula (Ⅰ) to the additive is 0.2–1.5:1.0.

[0019] The beneficial effects of this invention are as follows:

[0020] 1) The reaction conditions are mild, and inexpensive and readily available raw materials are used to efficiently promote the preparation of thioether compounds;

[0021] 2) The substrates have wide applicability and can yield the corresponding thioether compounds in good yields;

[0022] 3) The operation process is simple and efficient. Detailed Implementation

[0023] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0024] Example 1: Preparation of thioethers

[0025]

[0026] In a 100 mL single-necked flask, 3.53 g (20 mmol) of benzenesulfonyl chloride, 0.88 g of palladium acetate, 2.65 g of 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthracene, 3.53 g (19 mmol) of cuprous iodide, 3.53 g (61 mmol) of potassium fluoride, and 40 mL of 1,4-dioxane as solvent were added sequentially. The mixture was stirred at 130 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added for dilution, followed by extraction three times with 50 mL of ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 1.69 g of sulfide with a purity of 99% and a yield of 90%.

[0027] 1H NMR spectrum: (400MHz, Chloroform-d) δ 7.29–7.13 (m, 10H).

[0028] Example 2: Preparation of 4,4'-dimethyl sulfide

[0029]

[0030] In a 100 mL single-necked flask, 3.81 g (20 mmol) of p-toluenesulfonyl chloride, 0.95 g of palladium chloride diacetonitrile, 2.86 g of 1,3-bis(diphenylphosphine)propane, 3.81 g (27 mmol) of cuprous bromide, 3.81 g (91 mmol) of sodium fluoride, and 40 mL of 1,4-dioxane were added sequentially as solvent. The mixture was stirred at 150 °C for 14 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added for dilution, followed by extraction three times with 50 mL of ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 1.99 g of 4,4'-dimethyl sulfide with a purity of 99% and a yield of 92%.

[0031] 1H NMR spectrum: (400MHz, Chloroform-d) δ 7.23 (d, J = 8.3Hz, 4H), 7.10 (d, J = 8.1Hz, 4H), 2.32 (s, 6H).

[0032] Example 3: Preparation of 4,4-di-tert-butyl sulfide

[0033]

[0034] In a 100 mL single-necked flask, 4.65 g (20 mmol) of p-tert-butylbenzenesulfonyl chloride, 1.16 g of palladium trifluoroacetate, 3.49 g of 1,1'-bis(diphenylphosphine)ferrocene, 4.65 g (63 mmol) of trimethylsilane, 4.65 g (34 mmol) of potassium carbonate, and 40 mL of 1,4-dioxane were added sequentially as solvent. The mixture was stirred at 135 °C for 13 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added for dilution, followed by extraction three times with 50 mL of ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 2.74 g of 4,4-di-tert-butyl sulfide with a purity of 99% and a yield of 91%.

[0035] 1H NMR spectrum: (400MHz, Chloroform-d) δ 7.34–7.30 (m, 4H), 7.28–7.26 (m, 4H), 1.30 (s, 18H).

[0036] Example 4: 4,4-Difluorosulfide

[0037]

[0038] In a 100 mL round-bottom flask, 3.89 g (20 mmol) of p-fluorobenzenesulfonyl chloride, 0.97 g of palladium acetate, 2.92 g of 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthracene, 3.89 g (20 mmol) of cuprous iodide, 3.89 g (67 mmol) of potassium fluoride, and 40 mL of 1,4-dioxane were added sequentially as solvent. The mixture was stirred at 145 °C for 15 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added for dilution, followed by extraction three times with 50 mL of ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 2.02 g of 4,4-difluorosulfide with a purity of 99% and a yield of 90%.

[0039] 1H NMR spectrum: (400MHz, Chloroform-d) δ 7.34–7.27 (m, 4H), 7.04–6.97 (m, 4H).

[0040] Example 5: Preparation of 4,4-dichlorosulfide

[0041]

[0042] In a 100 mL single-necked flask, 4.22 g (20 mmol) of p-chlorobenzenesulfonyl chloride, 1.06 g of palladium chloride diacetonitrile, 3.17 g of 1,3-bis(diphenylphosphine)propane, 4.22 g (29 mmol) of cuprous bromide, and 4.22 g (101 mmol) of sodium fluoride were added sequentially. 40 mL of 1,4-dioxane was used as a solvent. The mixture was stirred at 140 °C for 14 h under a nitrogen atmosphere. After the reaction was complete, 50 mL of water was added for dilution, followed by extraction three times with 50 mL of ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 2.32 g of 4,4-dichlorosulfide with a purity of 99% and a yield of 90%.

[0043] 1H NMR spectrum: (400MHz, Chloroform-d) δ 7.31–7.23 (m, 8H).

[0044] Example 6: Preparation of 4,4-dibromosulfide

[0045]

[0046] In a 100 mL single-necked flask, 5.11 g (20 mmol) of p-bromobenzenesulfonyl chloride, 1.28 g of palladium trifluoroacetate, 3.83 g of 1,1'-bis(diphenylphosphine)ferrocene, 5.11 g (69 mmol) of trimethylsilane, 5.11 g (37 mmol) of potassium carbonate, and 40 mL of 1,4-dioxane were added sequentially as solvent. The mixture was stirred at 135 °C for 13 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added for dilution, followed by extraction three times with 50 mL of ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 3.13 g of 4,4-dibromosulfide with a purity of 99% and a yield of 90%.

[0047] 1H NMR spectrum: (400MHz, Chloroform-d) δ 7.45–7.41 (m, 4H), 7.23–7.12 (m, 4H).

[0048] Example 7: 4,4-Difluoromethyl sulfide

[0049]

[0050] In a 100 mL single-necked flask, 4.89 g (20 mmol) of p-trifluoromethylbenzenesulfonyl chloride, 1.22 g of palladium acetate, 3.67 g of 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthracene, 4.89 g (26 mmol) of cuprous iodide, 4.89 g (84 mmol) of potassium fluoride, and 40 mL of 1,4-dioxane were added sequentially as solvent. The mixture was stirred at 145 °C for 15 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added for dilution, followed by extraction three times with 50 mL of ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 2.99 g of 4,4-ditrifluoromethyl sulfide with a purity of 99% and a yield of 92%.

[0051] 1H NMR spectrum: (400MHz, Chloroform-d) δ 7.39-7.32 (m, 4H), 7.17 (ddt, J = 7.6, 2.0, 1.0Hz, 4H).

Claims

1. A method for preparing diphenyl sulfide compounds from arylsulfonyl chlorides, characterized by, The process includes the following steps: using a sulfonyl chloride compound as shown in formula (I) as a raw material, a catalyst, ligand, additive, base, and solvent are added to a reactor, and the reaction is carried out under a nitrogen atmosphere to obtain a diphenyl sulfide compound as shown in formula (II). The reaction equation is as follows: ， In this process, the H on the benzene ring is either substituted or unsubstituted by a substituent R, and when substituted, R is fluorine, chlorine, bromine, methyl, tert-butyl or trifluoromethyl. The catalyst is palladium acetate, palladium diacetonitrile chloride, or palladium trifluoroacetate; The ligands are 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthracene, 1,3-bis(diphenylphosphine)propane or 1,1'-bis(diphenylphosphine)ferrocene; The additives are cuprous iodide, cuprous bromide or trimethylsilane.

2. The method as described in claim 1, characterized in that, The solvent is N,N-dimethylformamide, 1,4-dioxane or toluene, and the base is potassium fluoride, sodium fluoride or potassium carbonate.

3. The method as described in claim 1, characterized in that, The reaction time is 12-15 hours, and the reaction temperature is 130-150℃.

4. The method as described in claim 1, characterized in that, The molar ratio of the sulfonyl chloride compound shown in formula (Ⅰ) to the catalyst is 3.0~6.0:1.

0.

5. The method as described in claim 1, characterized in that, The molar ratio of the sulfonyl chloride compound to the ligand shown in formula (Ⅰ) is 2.5~4.5:1.

0.

6. The method as described in claim 2, characterized in that, The molar ratio of the sulfonyl chloride compound to the base shown in formula (Ⅰ) is 0.1~1.0:1.

0.

7. The method as described in claim 1, characterized in that, The molar ratio of the sulfonyl chloride compound shown in formula (Ⅰ) to the additive is 0.2~1.5:1.0.

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