Method for preparing thioether compound from thiosulfate

Abstract

The invention discloses a method for preparing a thioether compound from thiosulfate, which comprises the following steps: taking thiosulfate as a raw material, sequentially adding a catalyst, a ligand, an additive, alkali and a solvent into a reactor, and reacting in a nitrogen atmosphere to prepare the thioether compound as shown in a formula (II), h on a benzene ring is substituted or not substituted by a substituent R1, R1 is methyl during substitution, and a substituent R2 is benzyl, 4-chlorphenyl, 4-nitrophenyl, 4-methoxyphenyl, 2-fluorophenyl, methyl or benzyl. The method has the advantages of mild reaction conditions, use of cheap and easily available raw materials, and efficient promotion of the preparation of thioether compounds.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical organic synthesis, and particularly relates to a method for preparing thioether compounds from thiosulfate. Background Art

[0002] Nowadays, the construction of C-S bonds is a major research topic in organic chemistry. This is because sulfur-containing compounds such as sulfonyl chlorides, thiosulfates, thioethers, thiols and disulfides are an important class of structures. They are of great value in the development of drugs, pesticides and functional organic molecules. The following synthetic schemes have been developed for the construction of C-S bonds: 1. Cross-coupling between aromatic thiols and halide or borate derivatives; 2. CH activation with directing groups. Nevertheless, these methods have certain defects. These defects include: the use of expensive iodobenzene or phenylboronic acid analogs, pungent odor and limited substrate range. Summary of the invention

[0003] The present invention aims at the defects in the prior art and provides a method for preparing thioether compounds from thiosulfate.

[0004] In order to achieve the above purpose, the following technical solutions are adopted:

[0005] A method for preparing a thioether compound from a thiosulfate ester comprises the following steps: using a thiosulfate ester as shown in formula (I) as a raw material, sequentially adding a catalyst, a ligand, an additive, a base, and a solvent into a reactor, reacting in a nitrogen atmosphere to obtain a thioether compound as shown in formula (II), and the reaction equation is as follows:

[0006]

[0007] In the formula, H on the benzene ring is substituted by a substituent R1 or not, when substituted, R1 is a methyl group, and the substituent R2 is a benzyl group, 4-chlorophenyl, 4-nitrophenyl, 4-methoxyphenyl, 2-fluorophenyl, methyl or benzyl group.

[0008] Furthermore, the catalyst is palladium acetate, diacetonitrile palladium chloride or palladium trifluoroacetate, and the ligand is 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 1,3-bis(diphenylphosphino)propane or 1,1'-bis(diphenylphosphino)ferrocene.

[0009] Furthermore, the base is potassium fluoride, sodium fluoride or potassium carbonate, and the additive is cuprous iodide, cuprous bromide or trimethylsilane.

[0010] Furthermore, the reaction temperature is 130-150° C., and the reaction time is 12-15 hours.

[0011] Furthermore, the molar ratio of the thiosulfate ester represented by formula (I) to the catalyst is 3.0-7.5:1.0.

[0012] Furthermore, the molar ratio of the thiosulfate ester represented by formula (I) to the ligand is 1.5-4.0:1.0.

[0013] Furthermore, the molar ratio of the thiosulfate ester and the base as shown in formula (I) is 0.1-0.6:1.0.

[0014] Furthermore, the molar ratio of the thiosulfate ester represented by formula (I) to the additive is 0.2-0.8:1.0.

[0015] The beneficial effects of the present invention are mainly reflected in:

[0016] 1. The reaction conditions are mild, and cheap and readily available raw materials are used to efficiently promote the preparation of sulfide compounds.

[0017] 2. The substrate has wide applicability and can obtain the corresponding asymmetric sulfide compounds in good yield.

[0018] 3. The operation process is simple and efficient. DETAILED DESCRIPTION

[0019] The present invention is further described below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto.

[0020] Example 1: Preparation of p-methyl diphenyl sulfide

[0021]

[0022] In a 100 mL single-necked flask, 5.29 g (20 mmol) of S-phenyl-4-methylbenzenesulfonyl thioester, 1.32 g of palladium acetate, 3.97 g of 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthene, 5.29 g (71 mmol) of trimethylsilane, 5.29 g (38 mmol) of potassium carbonate, and 40 mL of 1,4-dioxane as solvent were added in sequence, and stirred at 135 ° C for 13 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added to dilute, and then 50 mL of ethyl acetate was added to extract three times. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 3.64 g of p-methyl diphenyl sulfide with a purity of 99% and a yield of 90%.

[0023] H NMR: (400 MHz, CDCl3) δ7.41-7.35 (m, 3H), 7.33-7.27 (m, 2H), 7.12 (dd, J = 14.3, 8.1 Hz, 4H), 2.32 (s, 3H).

[0024] Example 2: Preparation of p-methyl-p-chlorodiphenyl sulfide

[0025]

[0026] In a 100 mL single-necked flask, 5.98 g (20 mmol) of S-(4-chloro)-phenyl-4-methylbenzenesulfonyl thioester, 1.49 g of diacetonitrile palladium chloride, 4.48 g of 1,3-bis(diphenylphosphino)propane, 5.98 g (31 mmol) of cuprous iodide, 5.98 g (103 mmol) of potassium fluoride, and 40 mL of 1,4-dioxane as solvent were added in sequence, and stirred at 145 ° C for 15 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added to dilute, and then 50 mL of ethyl acetate was added to extract three times. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 4.36 g of p-methyl-p-chlorodiphenyl sulfide with a purity of 99% and a yield of 92%.

[0027] H NMR: (400 MHz, CDCl3) δ7.46-7.42 (m, 4H), 7.30 (d, J = 8.5 Hz, 4H), 2.34 (s, 3H).

[0028] Example 3: Preparation of p-methyl-p-nitrodiphenyl sulfide

[0029]

[0030] In a 100 mL single-necked flask, 6.19 g (20 mmol) of S-(4-nitro)-phenyl-4-methylbenzenesulfonyl sulfide, 1.55 g of palladium trifluoroacetate, 4.64 g of 1,1'-bis(diphenylphosphino)ferrocene, 6.19 g (43 mmol) of cuprous bromide, 6.19 g (147 mmol) of sodium fluoride, and 40 mL of 1,4-dioxane as solvent were added in sequence, and stirred at 130 ° C for 13 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added to dilute, and then 50 mL of ethyl acetate was added to extract three times. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 4.51 g of p-methyl-p-nitrodiphenyl sulfide with a purity of 99% and a yield of 91%. H NMR: (600 MHz, CDCl3) δ8.09-8.04 (m, 2H), 7.48-7.44 (m, 2H), 7.32-7.27 (m, 2H), 7.18-7.13 (m, 2H), 2.44 (s, 3H).

[0031] Example 4: Preparation of p-methoxy-p-methyl diphenyl sulfide

[0032]

[0033] In a 100 mL single-necked flask, 5.89 g (20 mmol) of S-(4-methoxy)-phenyl-4-methylbenzenesulfonyl thioester, 1.47 g of palladium acetate, 4.42 g of 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthene, 5.89 g (79 mmol) of trimethylsilane, 5.89 g (43 mmol) of potassium carbonate, and 40 mL of 1,4-dioxane as solvent were added in sequence, and stirred at 150 ° C for 12 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added to dilute, and then 50 mL of ethyl acetate was added to extract three times. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 4.19 g of p-methoxy-p-methyl diphenyl sulfide with a purity of 99% and a yield of 90%.

[0034] H NMR: (400 MHz, CDCl3) δ7.40-7.37 (m, 2H), 7.17-7.14 (m, 2H), 7.12-7.05 (m, 2H), 6.92-6.86 (m, 2H), 3.83 (s, 3H), 2.32 (s, 3H).

[0035] Example 5: Preparation of o-fluoro-p-methylphenyl diphenyl sulfide

[0036]

[0037] In a 100 mL single-necked flask, 5.67 g (20 mmol) of S-(2-fluoro)-phenyl-4-methylbenzenesulfonyl thioester, 1.42 g of diacetonitrile palladium chloride, 4.25 g of 1,3-bis(diphenylphosphino)propane, 5.67 g (30 mmol) of cuprous iodide, 5.67 g (98 mmol) of potassium fluoride, and 40 mL of 1,4-dioxane as solvent were added in sequence, and stirred at 130 ° C for 12 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added to dilute, and then 50 mL of ethyl acetate was added to extract three times. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 3.99 g of o-fluoro-p-methyl diphenyl sulfide with a purity of 99% and a yield of 90%.

[0038] H NMR: (400 MHz, CDCl3) δ7.30 (d, J = 8.3 Hz, 2H), 7.13 (td, J = 7.8, 1.7 Hz, 4H), 7.07-7.02 (m, 2H), 2.35 (s, 3H).

[0039] Example 6: Preparation of methyl phenyl sulfide

[0040]

[0041] In a 100 mL single-necked flask, 3.74 g (20 mmol) of p-S-methyl-benzenesulfonyl sulfide, 0.94 g of palladium trifluoroacetate, 2.81 g of 1,1'-bis(diphenylphosphino)ferrocene, 3.74 g (28 mmol) of cuprous bromide, 3.74 g (96 mmol) of sodium fluoride, and 40 mL of 1,4-dioxane as solvent were added in sequence, and stirred at 150 ° C for 14 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added to dilute, and then 50 mL of ethyl acetate was added to extract three times. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 2.29 g of p-methylphenyl sulfide with a purity of 99% and a yield of 92%.

[0042] H NMR: (600 MHz, CDCl3) δ7.32 (d, J = 2.2 Hz, 2H), 7.29 (dd, J = 3.8, 1.9 Hz, 1H), 7.17 (tt, J = 6.5, 1.9 Hz, 2H).

[0043] Example 7: Preparation of p-methylbenzylphenyl sulfide

[0044]

[0045] In a 100 mL single-necked flask, 5.57 g (20 mmol) of S-benzyl-4-methylbenzenesulfonate, 1.39 g of palladium acetate, 4.17 g of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 5.57 g (75 mmol) of trimethylsilane, 5.57 g (40 mmol) of potassium carbonate, and 40 mL of 1,4-dioxane as solvent were added in sequence, and stirred at 135 ° C for 13 h under a nitrogen atmosphere. After the reaction was completed, 50 mL of water was added to dilute, and then 50 mL of ethyl acetate was added to extract three times. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 3.94 g of p-methylbenzylphenyl sulfide with a purity of 99% and a yield of 91%.

[0046] H NMR: (400 MHz, CDCl3) δ7.27-7.20 (m, 2H), 7.19-7.12 (m, 5H), 6.99 (d, J=8.3 Hz, 2H), 4.00 (s, 2H), 2.23 (s, 3H).

Claims

1. A method for preparing thioether compounds from thiosulfate, characterized in that: The method comprises the following steps: using a thiosulfate ester as shown in formula (I) as a raw material, sequentially adding a catalyst, a ligand, an additive, a base, and a solvent into a reactor, reacting in a nitrogen atmosphere to obtain a sulfide compound as shown in formula (II), and the reaction equation is as follows: In the formula, H on the benzene ring is substituted by a substituent R1 or not, when substituted, R1 is a methyl group, and the substituent R2 is a benzyl group, 4-chlorophenyl, 4-nitrophenyl, 4-methoxyphenyl, 2-fluorophenyl, methyl or benzyl group.

2. The method according to claim 1, characterized in that The catalyst is palladium acetate, diacetonitrile palladium chloride or palladium trifluoroacetate, and the ligand is 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 1,3-bis(diphenylphosphino)propane or 1,1'-bis(diphenylphosphino)ferrocene.

3. The method according to claim 1, characterized in that The base is potassium fluoride, sodium fluoride or potassium carbonate, and the additive is cuprous iodide, cuprous bromide or trimethylsilane.

4. The method according to claim 1, characterized in that The reaction temperature is 130-150°C and the reaction time is 12-15h.

5. The method according to claim 1, characterized in that The molar ratio of the thiosulfate ester represented by formula (I) to the catalyst is 3.0-7.5:1.

0.

6. The method according to claim 1, characterized in that The molar ratio of the thiosulfate ester and the ligand as shown in formula (I) is 1.5-4.0:1.

0.

7. The method according to claim 1, characterized in that The molar ratio of the thiosulfate ester and the base as shown in formula (I) is 0.1-0.6:1.

0.

8. The method according to claim 1, characterized in that The molar ratio of the thiosulfate ester represented by formula (I) to the additive is 0.2-0.8:1.0.

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