Preparation method of compound containing diphenyl sulfide

Abstract

The invention relates to a method for preparing a diphenyl sulfide-containing compound as shown in a general formula (I). The reaction formula is as follows: each group in a # imgabs0 # formula is shown in the specification. According to the method, biphenyl shown in the general formula (IV) is subjected to sulfonylation, reduction and etherification reactions, and the biphenyl-containing thioether compound shown in the general formula I can be prepared with high yield.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a biphenyl sulfide compound. Background Art

[0002] Biphenyl sulfide compounds are a class of highly efficient new acaricides. CN105541682A discloses biphenyl sulfide compounds as shown in its general formula I, and these compounds exhibit excellent acaricidal activity against Tetranychus cinnabarinus.

[0003]

[0004] CN105541682A reported the synthesis method of this type of compound. Aryl iodobenzene is coupled with a palladium catalyst under the action of a suitable base in a suitable organic solvent to obtain the target product. The specific reaction formula is as follows:

[0005]

[0006] CN111100048A discloses the synthesis method of this type of compound. Biphenyl is subjected to four-step reactions of sulfonylation, reduction, hydrolysis, and etherification to obtain the biphenyl sulfide compound shown in general formula I. The specific reaction formula is as follows:

[0007]

[0008] All along, technicians have been committed to continuously researching and developing new, more advanced, reasonable, and more environmentally friendly preparation methods in order to obtain highly efficient and safe biphenyl sulfide acaricides with better quality and lower prices. Summary of the Invention

[0009] The purpose of the present invention is to provide a preparation method of a biphenyl sulfide compound suitable for large-scale industrial production.

[0010] To achieve the above purpose, the technical solution adopted by the present invention is:

[0011] A preparation method of a biphenyl sulfide compound, through three-step reactions of sulfonylation, reduction, and etherification of biphenyl shown in general formula (IV), to obtain a biphenyl sulfide compound shown in general formula (I) with a high yield. The reaction formula is as follows:

[0012]

[0013] In the formula: R is C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 2 -C 8 alkenyl, C 2 -C8 haloalkenyl, C 2 -C 8 alkynyl, C 2 -C 8 haloalkynyl.

[0014] Specifically:

[0015] (1) Preparation of compound (III): The biphenyl represented by general formula (IV) reacts with sulfuric acid and thionyl chloride in the range of -10°C to 100°C for a reaction time of 0.5 - 24 hours to obtain the biphenylsulfonyl chloride compound represented by general formula (III); wherein, the molar ratio of the biphenyl represented by general formula (IV) to sulfuric acid and thionyl chloride is 1:2 - 6:4 - 40;

[0016] (2) Preparation of compound (II): The compound represented by general formula (III) is reduced with zinc powder or iron powder in a suitable solvent A under the action of an acid to obtain the biphenylthiol compound represented by general formula (II);

[0017] (3) Preparation of compound (I): The thiol represented by general formula (II) reacts with a halogenating agent in a suitable solvent B under the action of a base for 0.5 - 24 hours to obtain the biphenyl sulfide compound represented by general formula (I).

[0018] In the step (2), the molar ratio of the compound represented by general formula (III) to zinc powder or iron powder is 1:5 - 20, the reaction temperature is from 0°C to the boiling point of solvent A, the reaction time is 0.5 - 24 hours, the acid is sulfuric acid or hydrochloric acid, the molar ratio of the compound represented by general formula (III) to sulfuric acid is 1:5 - 12, and the molar ratio of the compound represented by general formula (III) to hydrochloric acid is 1:10 - 24;

[0019] In the step (3), the molar ratio of the thiol represented by general formula (II) to the halogenating agent and the base is 1:2 - 6:1 - 6, and the reaction temperature ranges from 0°C to the boiling point of solvent B.

[0020] Furthermore,

[0021] (1) Preparation of compound (III): The molar ratio of the biphenyl represented by general formula (IV) to sulfuric acid and thionyl chloride is 1:2 - 4:4 - 20, the reaction temperature is in the range of 20°C to 100°C, and the reaction time is 2 - 16 hours;

[0022] (2) Preparation of compound (II): The compound represented by the general formula (III) is reduced with zinc powder or iron powder in a suitable solvent A under the action of an acid to obtain the compound represented by the general formula (II). The molar ratio of the compound represented by the general formula (III) to zinc powder or iron powder is 1:5 - 15, the reaction temperature is from 20°C to the boiling point of solvent A, the reaction time is 3 - 16 hours, the molar ratio of the compound represented by the general formula (III) to sulfuric acid is 1:5 - 10, and the molar ratio of the compound represented by the general formula (III) to hydrochloric acid is 1:10 - 20;

[0023] (3) Preparation of compound (I): The thiophenol represented by the general formula (II) reacts with a halogenating reagent in a suitable solvent B under the action of a base for 1 - 10 hours to obtain the biphenyl sulfide compound represented by the general formula (I). The molar ratio of the thiophenol represented by the general formula (II) to the halogenating reagent and the base is 1:2 - 4:1 - 4, and the reaction temperature is from 25°C to 90°C.

[0024] The suitable solvent A in the step (2) is selected from one or two of water, dichloromethane, dichloroethane, tetrahydrofuran, 2 - methyltetrahydrofuran, dioxane, and toluene.

[0025] The concentration of sulfuric acid in the step (2) is 20% to 80%, and the concentration of hydrochloric acid is 15% to 36%.

[0026] The suitable solvent B in the step (3) is selected from one or two of dichloromethane, dichloroethane, acetone, butanone, acetonitrile, tetrahydrofuran, 2 - methyltetrahydrofuran, DMF, DMSO, dioxane, ethyl acetate, and toluene.

[0027] The base in the step (3) is selected from potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium tert - butoxide, sodium methoxide, sodium ethoxide, sodium tert - butoxide, or sodium hydride.

[0028] The halogenating reagent in the step (3) is represented by the formula (i):

[0029] R’-X formula (i)

[0030] Wherein, R’ is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl; X is chlorine or bromine.

[0031] Advantages of the present invention compared with the prior art:

[0032] (1) Preparation of compound (III) in the preparation of the present invention: More inexpensive and readily available, and relatively safe sulfuric acid and thionyl chloride are used as sulfonylation raw materials to replace the original chlorosulfonic acid. On the one hand, the safety is improved, and on the other hand, the post-treatment operation is simplified and the yield is increased.

[0033] (2) Preparation of compound (II) in the preparation of the present invention: Metal (zinc or iron) is used to directly reduce sulfonyl chloride (III) to thiophenol (II) in one step under acidic conditions, reducing one hydrolysis reaction, and at the same time the yield is also improved.

[0034] (3) Preparation of biphenyl sulfide (I) in the present invention: Readily available bromo- or chloro-alkylating reagents are used to replace expensive iodine-containing and sulfonate alkylating reagents.

[0035] The present invention uses a biphenyl compound (IV) as a raw material, and through three-step reactions of sulfonylation, reduction, and etherification, a biphenyl sulfide compound is prepared in high yield. Therefore, the new method of the present invention is more suitable for large-scale industrial production. Detailed implementation mode

[0036] The following examples are used to illustrate in detail the preparation method of the general formula (I) shown in the present invention, but do not mean to limit the present invention. Various transformations and modifications can be carried out within the scope defined by the claims of the present invention.

[0037] Example 1:

[0038]

[0039]

[0040] Add thionyl chloride (48.1 g, 99%, 0.4 mol) to the reaction flask and stir. Dropwise add sulfuric acid (20 g, 8%, 0.2 mol) at room temperature, and the dropping time is about 0.5 - 1 h. After dropping, control the temperature not to exceed 25 °C, and dropwise add a mixture of the biphenyl compound (22.0 g, 99%, 0.1 mol) shown in formula (IV) and 50 ml of dichloroethane, and the dropping time is about 0.5 - 1 h. After the addition is complete, keep the temperature at 25 - 30 °C and react for 3 h. After passing the analysis, add 50 ml of water to the reaction flask, separate the layers, and the organic layer is dissolved and neutralized with saturated sodium bicarbonate, and concentrated to obtain 41.8 g of 2,2'-difluoro-4,4'-dimethyl-5,5'-disulfonyl chloride-1,1'-biphenyl (III), the HPLC quantitative content is 96.8%, and the yield is 97.5%.

[0041] Example 2:

[0042]

[0043] To the reaction flask were successively added the compound shown in formula (III) (41.8 g, 96.8%, 0.098 mol), dichloroethane (200 g), zinc powder (46.5 g, 95%, 0.68 mol). The temperature was raised to 50 - 60 °C, and 30% sulfuric acid (222.2 g) was added dropwise. After the addition was complete, the reaction was carried out under insulation for 4 h. After passing the analysis, the temperature was lowered, and the mixture was filtered and separated into layers. The organic layer was concentrated to obtain 27.2 g of biphenylthiol compound (II) with a content of 96.5% and a yield of 95.0%.

[0044] Example 3:

[0045]

[0046] To the reaction flask were successively added the compound shown in formula (II) (29.2 g, 96.5%, 0.1 mol), DMF (100 mL), sodium carbonate (21.4 g, 99%, 0.2 mol), 2-chloro-1,1,1-trifluoroethane (26.3 g, 0.22 mol). The temperature was raised to 35 - 40 °C, and the reaction was carried out under insulation for 3 h. After passing the analysis, the temperature was lowered, and the solvent was distilled off under reduced pressure. Toluene (100 mL) and water (100 mL) were added, and the mixture was extracted and separated into layers. The organic phase was distilled off toluene under reduced pressure. Ethanol (45 g) and water (10 g) were added to the residue, and the temperature was raised until completely dissolved. After cooling, a solid precipitated out. It was filtered and dried to obtain 42.0 g of 2,2'-difluoro-4,4'-dimethyl-5,5'-bis(2,2,2-trifluoroethylthio)-1,1'-biphenyl with an HPLC quantitative content of 98.1% and a yield of 92.4%.

[0047] Example 4:

[0048]

[0049] To the reaction flask were successively added the compound shown in formula (II) (29.2 g, 96.5%, 0.1 mol), THF (100 mL), sodium carbonate (21.4 g, 99%, 0.2 mol), 1-bromo-2,2-difluoroethane (32.5 g, 0.22 mol). The temperature was raised to 30 - 35 °C, and the reaction was carried out under insulation for 3 h. After passing the analysis, the temperature was lowered, and the solvent was distilled off under reduced pressure. Toluene (100 mL) and water (100 mL) were added, and the mixture was extracted and separated into layers. The organic phase was distilled off toluene under reduced pressure. Ethanol (45 g) and water (10 g) were added to the residue, and the temperature was raised until completely dissolved. After cooling, a solid precipitated out. It was filtered and dried to obtain 38.6 g of 2,2'-difluoro-4,4'-dimethyl-5,5'-bis(2,2-difluoroethylthio)-1,1'-biphenyl with an HPLC quantitative content of 98.1% and a yield of 92.4%.

[0050] Example 5:

[0051] Synthesis of 2,2'-difluoro-4,4'-dimethyl-5,5'-bis(2,2,2-trifluoroethylthio)-1,1'-biphenyl (I)

[0052]

[0053] Into a 1000 L reactor, successively add the compound shown in formula (II) (145 Kg, 97.1%, 0.5 Kmol), THF (500 L), sodium carbonate (107 Kg, 99%, 1 Kmol), 2-chloro-1,1,1-trifluoroethane (132 Kg, 1.1 Kmol). Heat up to 35 - 40 °C and keep the temperature for reaction for 4 h. After analysis is qualified, cool down, distill off the solvent under reduced pressure, cool down, balance the negative pressure with nitrogen, add toluene (500 L), transfer the materials in the reactor to an extraction kettle, add water (500 L), extract and separate layers. Transfer the organic phase to a solvent stripping kettle, distill off toluene under reduced pressure, balance the negative pressure with nitrogen. Add ethanol (225 Kg) and water (50 Kg) to the residue, heat up to complete dissolution, and solid precipitates after cooling. Filter and dry to obtain 211 Kg of 2,2'-difluoro-4,4'-dimethyl-5,5'-bis(2,2,2-trifluoroethylthio)-1,1'-biphenyl. The HPLC quantitative content is 98.3% and the yield is 93.0%.

[0054] According to the above specific preparation method, other compounds shown in the following table can also be prepared using suitable raw materials.

[0055]

[0056]

Claims

1. A method for preparing a biphenyl sulfide-containing compound, characterized in that: The biphenyl represented by the general formula (IV) is subjected to three steps of sulfonylation, reduction and etherification to obtain a biphenyl sulfide compound represented by the general formula (I) in high yield. The reaction formula is as follows: In the formula: R is C1-C8 alkyl, C1-C8 haloalkyl, C2-C8 alkenyl, C2-C8 haloalkenyl, C2-C8 alkynyl, C2-C8 haloalkynyl.

2. The method for preparing a biphenyl sulfide-containing compound according to claim 1, characterized in that: (1) Preparation of compound (III): Biphenyl represented by general formula (IV) is reacted with sulfuric acid and thionyl chloride at a temperature ranging from -10°C to 100°C for a reaction time of 0.5-24 hours to obtain a biphenylsulfonyl chloride compound represented by general formula (III); wherein the molar ratio of biphenyl represented by general formula (IV) to sulfuric acid and thionyl chloride is 1:2-6:4-40; (2) Preparation of compound (II): The compound represented by general formula (III) is reduced with zinc powder or iron powder in a suitable solvent A under the action of an acid to obtain a biphenylthiophenol compound represented by general formula (II); (3) Preparation of compound (I): The thiophenol represented by the general formula (II) and the halogenating agent are reacted in a suitable solvent B under the action of a base for 0.5-24 hours to obtain a biphenyl sulfide compound represented by the general formula (I).

3. The method for preparing a biphenyl sulfide-containing compound according to claim 2, characterized in that: In the step (2), the molar ratio of the compound represented by the general formula (III) to the zinc powder or iron powder is 1:5-20, the reaction temperature is 0°C to the boiling point of the solvent A, the reaction time is 0.5-24 hours, the acid is sulfuric acid or hydrochloric acid, the molar ratio of the compound represented by the general formula (III) to sulfuric acid is 1:5-12, and the molar ratio of the compound represented by the general formula (III) to hydrochloric acid is 1:10-24; In the step (3), the molar ratio of the thiophenol represented by the general formula (II) to the halogenating agent and the base is 1:2-6:1-6, and the reaction temperature is from 0°C to the boiling point of the solvent B.

4. The method for preparing a biphenyl sulfide-containing compound according to any one of claims 1 to 3, characterized in that: (1) Preparation of compound (III): The molar ratio of biphenyl represented by general formula (IV) to sulfuric acid and thionyl chloride is 1:2-4:4-20, the reaction temperature is in the range of 20°C to 100°C, and the reaction time is 2-16 hours; (2) Preparation of compound (II): The compound represented by general formula (III) is reduced with zinc powder or iron powder in a suitable solvent A under the action of an acid to obtain the compound represented by general formula (II), wherein the molar ratio of the compound represented by general formula (III) to zinc powder or iron powder is 1:5-15, the reaction temperature is from 20°C to the boiling point of solvent A, the reaction time is 3-16 hours, the molar ratio of the compound represented by general formula (III) to sulfuric acid is 1:5-10, and the molar ratio of the compound represented by general formula (III) to hydrochloric acid is 1:10-20; (3) Preparation of compound (I): The thiophenol represented by the general formula (II) and the halogenating agent are reacted in a suitable solvent B in the presence of a base for 1-10 hours to obtain a biphenyl sulfide compound represented by the general formula (I); the molar ratio of the thiophenol represented by the general formula (II) to the halogenating agent and the base is 1:2-4:1-4, and the reaction temperature is from 25°C to 90°C.

5. The method for preparing a biphenyl sulfide-containing compound according to claim 2, characterized in that: In the step (2), the suitable solvent A is selected from one or two of water, dichloromethane, dichloroethane, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane and toluene.

6. The method for preparing a biphenyl sulfide-containing compound according to claim 3, characterized in that: In the step (2), the concentration of sulfuric acid is 20% to 80%, and the concentration of hydrochloric acid is 15% to 36%.

7. The method for preparing a biphenyl sulfide-containing compound according to claim 2, characterized in that: In the step (3), the suitable solvent B is selected from one or two of dichloromethane, dichloroethane, acetone, butanone, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, DMF, DMSO, dioxane, ethyl acetate and toluene.

8. The method for preparing a biphenyl sulfide-containing compound according to claim 2, characterized in that: The base in step (3) is selected from potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium tert-butoxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide or sodium hydride.

9. The method for preparing a biphenyl sulfide-containing compound according to claim 2, characterized in that: The halogenating agent in step (3) is represented by formula (i): R'-X formula (i) Wherein, R' is C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl; X is chlorine or bromine.

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