PREPARATION METHOD OF SULFUR-CONTAINING BIPHENYL COMPOUND

Abstract

A preparation method of a sulfur-containing biphenylsulfur-containing biphenyl compound shown by the general formula (I) has a reaction formula as follows:

##STR00001##

Each substituent in the formula is defined in the description. In the method, halogeno benzene shown by the general formula (II) generates a coupling reaction in a catalytic system composed of a nickel compound and at least one ligand under the combined action of metallic zinc to obtain the sulfur-containing biphenyl compound shown by the general formula (I).

Claims

1. A preparation method of a sulfur-containing biphenyl compound, characterized in that: the method of the sulfur-containing biphenyl compound shown by the general formula (I) has a reaction formula as follows: ##STR00008## in the formula: R is selected from C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 haloalkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.2-C.sub.8 haloalkynyl; X is selected from chlorine or bromine; and m is selected from 0, 1 or 2.

2. The preparation method of the sulfur-containing biphenyl compound according to claim 1, characterized in that: the compound shown by the general formula (II) generates a coupling reaction in a catalytic system composed of a nickel compound and at least one ligand under the combined action of metallic zinc to obtain the compound shown by the general formula (I).

3. The preparation method of the sulfur-containing biphenyl compound according to claim 1, characterized in that: reaction conditions are: the compound shown by the general formula (II), the nickel compound, the ligand and the metallic zinc generate the coupling reaction for 1-24 hours in a suitable solvent at a temperature of 20° C. to a boiling point of the selected solvent, to obtain the compound shown by the general formula (I).

4. The preparation method of the sulfur-containing biphenyl compound according to claim 3, characterized in that: the solvent is selected from toluene, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, acetone, butanone, dimethyl formamide or dimethyl sulfoxide.

5. The preparation method of the sulfur-containing biphenyl compound according to claim 1, characterized in that: an activation additive is added in the coupling reaction, and the addition amount of the activation additive is 1%-15% of the molar weight of the compound shown by the general formula (II), wherein the activation additive is metal halide, metal sulfate or metal phosphate, and the metal in the activation additive is alkali metal, alkaline earth metal, manganese or aluminum.

6. The preparation method of the sulfur-containing biphenyl compound according to claim 1, characterized in that: the nickel compound is selected from nickel chloride, nickel bromide, bis(triphenylphosphine) nickel chloride or bis(triphenylphosphine) nickel bromide; the addition amount of the nickel compound is 1%40% of the molar weight of the compound shown by the general formula (II); the ligand is selected from triarylphosphine, wherein aryl is selected from C.sub.6-C.sub.34 aryl; the addition amount of the ligand is 20%-100% of the molar weight of the compound shown by the general formula (II); and the amount of the metallic zinc is 50%-200% of the molar weight of the compound shown by the general formula (II).

7. The preparation method of the sulfur-containing biphenyl compound according to claim 6, characterized in that: the nickel compound is selected from nickel chloride; the addition amount of the nickel compound is 2%-5% of the molar weight of the compound shown by the general formula (II); the ligand is selected from triphenylphosphine; the addition amount of the ligand is 40%-60% of the molar weight of the compound shown by the general formula (II); the activation additive is selected from halogenated substances of alkali metal; the addition amount of the activation additive is 5%-10% of the molar weight of the compound shown by the general formula (II); and the amount of the metallic zinc is 100%-150% of the molar weight of the compound shown by the general formula (II).

8. The preparation method of the sulfur-containing biphenyl compound according to claim 7, characterized in that: the activation additive is selected from sodium bromide, potassium bromide, sodium iodide or potassium iodide.

Description

EXAMPLES

[0023] The following Examples are used to describe the preparation method of the general formula (I) shown in the present invention in detail, but are not used to limit the present invention. Various changes and modifications can be made within the scope defined by the claims of the present invention.

[0024] In the preparation process of the present invention, the substituted chlorobenzene or bromobenzene is coupled with cheap metallic zinc in a catalytic system composed of a cheap nickel compound and an organic phosphine ligand to prepare a sulfur-containing biphenyl compound shown by the general formula (I).

Example 1

Synthesis of 2,2′-difluoro-4,4′-dimethyl-5,5′-bis(2,2,2-trifluoroethylthio)-1,1′-biphenyl

[0025] ##STR00004##

[0026] Triphenylphosphine (13.23 g, 0.05 moL), sodium bromide (1.55 g, 0.015 moL), zinc powder (6.56 g, 0.1 moL) and nickel chloride (0.65 g, 0.005 moL) were added to a reaction flask. Nitrogen was introduced to replace the air. Under the conditions of room temperature and nitrogen protection, 12.5 mL of DMF was dropped into the reaction flask for 5 min without stirring; the material partially turned red; then, 50 mL of DMF was added. The reaction mixture was heated to 60° C. and stirred for 1 h. A mixture (30.9 g, dissolved in 15 mL of DMF) of 2-fluoro-4-methyl-5-trifluoroethylthiobromobenzene (30.9 g, 0.1 moL) and DMF was added dropwise for about 2 h. After adding, the temperature was kept at 40-45° C. until the reaction was completed. After the reaction was ended, the reaction mixture was cooled and filtered (under filtration aiding by diatomite). After the filtrate was concentrated under reduced pressure, 50 mL of toluene and 50 mL of water were added, and the mixture was stood for layering. An organic layer was transferred to a reaction flask and cooled in ice water bath. Hydrogen peroxide (5.7 g, 0.05 moL) was added dropwise into the organic layer for about 0.5 h. After adding, the temperature was kept at 40° C. for 1 h, and the reaction mixture was sampled and analyzed. When the triphenylphosphine completely converted into triphenylphosphine oxide, the temperature was cooled to room temperature, then the triphenylphosphine oxide was filtered out. The filter cake was washed with toluene (15 mL), the filtrate was layered. The toluene was removed under reduced pressure, then added 15 g of ethanol, the temperature was increased until all solids were dissolved, the solution was cooled with ice water bath to be below 10° C. The solids were continuously precipitated out, then filtered and dried to obtain 19.15 g of target compound which is white solid, with a melting point of 64.2-65.1° C. The HPLC quantitative content is 99%, and the yield is 85%. .sup.1H NMR (300 MHz, CDCl.sub.3): 7.55 (t, 2H), 7.06 (t, 2H), 3.33 (q, 4H), 2.52 (s, 6H). [M]=446.6 (GC-MS).

Example 2

Synthesis of 2,2′-difluoro-4,4′-dimethyl-5,5′-bis(2,2,2-trifluoroethylthio)-1,1′-biphenyl

[0027] ##STR00005##

[0028] Triphenylphosphine (13.23 g, 0.05 moL), potassium iodide (1.64 g, 0.01 moL), zinc powder (6.56 g, 0.1 moL) and nickel chloride (0.65 g, 0.005 moL) were added to the reaction flask. Nitrogen was introduced to replace the air. Under the conditions of room temperature and nitrogen protection, 12.5 mL of DMF was dropped into the reaction flask for 5 min without stirring; the material partially turned red; then, 50 mL of DMF was added. The reaction mixture was heated to 40° C. and stirred for 1 h. A mixture (26.1 g, dissolved in 15 mL of DMF) of 2-fluoro-4-methyl-5-trifluoroethylthiochlorobenzene (26.1 g, 0.1 moL) and DMF was added dropwise for about 2 h. After adding, the temperature was kept at 55-60° C. until the reaction was completed. After the reaction was ended, the reaction mixture was cooled and filtered (under filtration aiding by diatomite). After the filtrate was concentrated under reduced pressure, 50 mL of toluene and 50 mL of water were added, and the mixture was stood for layering. An organic layer was transferred to a reaction flask and cooled in ice water bath. Hydrogen peroxide (5.7 g, 0.05 moL) was added dropwise into the organic layer for about 0.5 h. After adding, the temperature was kept at 40° C. for 1 h, and the reaction mixture was sampled and analyzed. When the triphenylphosphine completely converted into triphenylphosphine oxide, the temperature was cooled to room temperature, then the triphenylphosphine oxide was filtered out. The filter cake was washed with toluene (15 mL), the filtrate was layered. The toluene was removed under reduced pressure, then added 14 g of ethanol, the temperature was increased until all solids were dissolved, the solution was cooled with ice water bath to be below 10° C. The solids were continuously precipitated out, then filtered and dried to obtain 18.66 g of target compound which is white solid, with a melting point of 64.2-65.1° C. The HPLC quantitative content is 98%, and the yield is 82%. .sup.1H NMR (300 MHz, CDCl.sub.3): 7.55 (t, 2H), 7.06 (t, 2H), 3.33 (q, 4H), 2.52 (s, 6H). [M]=446.6 (GC-MS).

Example 3

Synthesis of 2,2′-difluoro-4,4′-dimethyl-5,5′-bis(2,2,2-trifluoroethylthio)-1,1′-biphenyl

[0029] ##STR00006##

[0030] Triphenylphosphine (13.23 g, 0.05 moL), sodium iodide (0.75 g, 0.005 moL), zinc powder (6.56 g, 0.1 moL) and nickel bromide (1.09 g, 0.005 moL) were added into the reaction flask. Nitrogen was introduced to replace the air. Under the conditions of room temperature and nitrogen protection, 12.5 mL of DMF was dropped into the reaction flask for 5 min without stirring; the material partially turned red; then, 50 mL of DMF was added. The reaction mixture was heated to 40° C. and stirred for 1 h. A mixture (26.1 g, dissolved in 15 M1 of DMF) of 2-fluoro-4-methyl-5-trifluoroethylthiochlorobenzene (26.1 g, 0.1 moL) and DMF was added dropwise for about 2 h. After adding, the temperature was kept at 50-55° C. until the reaction was completed. After the reaction was ended, the reaction mixture was cooled and filtered (under filtration aiding by diatomite). After the filtrate was concentrated under reduced pressure, 50 mL of toluene and 50 mL of water were added, and the mixture was stood for layering. An organic layer was transferred to a reaction flask and cooled in ice water bath. Hydrogen peroxide (5.7 g, 0.05 moL) was added dropwise into the organic layer for about 0.5 h. After adding, the temperature was kept at 40° C. for 1 h, and the reaction mixture was sampled and analyzed. When the triphenylphosphine completely converted into triphenylphosphine oxide, the temperature was cooled to room temperature, then the triphenylphosphine oxide was filtered out. The filter cake was washed with toluene (15 mL), the filtrate was layered. The toluene was removed under reduced pressure, then added 15 g of ethanol, the temperature was increased until all solids were dissolved, the solution was cooled with ice water bath to be below 10° C. The solids were continuously precipitated out, then filtered and dried to obtain 18.90 g of target compound which is white solid, with a melting point of 64.2-65.1° C. The HPLC quantitative content is 98%, and the yield is 83%. .sup.1H NMR (300 MHz, CDCl.sub.3): 7.55 (t, 2H), 7.06 (t, 2H), 3.33 (q, 4H), 2.52 (s, 6H). [M]=446.6 (GC-MS).

Example 4

Synthesis of 2,2′-difluoro-4,4′-dimethyl-5,5′-bis(2,2,2-trifluoroethylthio)-1,1′-biphenyl

[0031] ##STR00007##

[0032] Triphenylphosphorus (534.7 g, 2 moL), sodium bromide (42.04 g, 0.4 moL), zinc powder (265.3 g, 4 moL) and nickel chloride (18.13 g, 0.14 moL) were added into the reaction flask. Nitrogen was introduced to replace the air. Under the conditions of room temperature and nitrogen protection, 1200 mL of DMF was dropped into the reaction flask for 30 min without stirring; the material partially turned red; then, 1200 mL of DMF was added. The reaction mixture was heated to 60° C. and stirred for 1 h. A mixture (1236 g, dissolved in 600 mL of DMF) of 2-fluoro-4-methyl-5-trifluoroethylthiobromobenzene (1236 g, 4 moL) and DMF was added dropwise for about 2 h. After adding, the temperature was kept at 40-45° C. until the reaction was completed. After the reaction was ended, the reaction mixture was cooled and filtered (under filtration aiding by diatomite). After the filtrate was concentrated under reduced pressure, 3000 mL of toluene and 2500 mL of water were added, and the mixture was stood for layering. An organic layer was transferred to a reaction flask and cooled in ice water bath. Hydrogen peroxide (226.7 g, 2 moL) was added dropwise into the organic layer for about 2 h. After adding, the temperature was kept at 40° C. for 1 h, and the reaction mixture was sampled and analyzed. When the triphenylphosphine completely converted into triphenylphosphine oxide, the temperature was cooled to room temperature, then the triphenylphosphine oxide was filtered out. The filter cake was washed with toluene (500 mL), the filtrate was layered. The toluene was removed under reduced pressure, then added 700 g of ethanol, the temperature was increased until all solids were dissolved, the solution was cooled with ice water bath to be below 10° C. The solids were continuously precipitated out, then filtered and dried to obtain 787.1 g of target compound which is white solid, with a melting point of 64.2-65.1° C. The HPLC quantitative content is 98.6%, and the yield is 87%. .sup.1H NMR (300 MHz, CDCl.sub.3): 7.55 (t, 2H), 7.06 (t, 2H), 3.33 (q, 4H), 2.52 (s, 6H). [M]=446.6 (GC-MS).

[0033] Meanwhile, according to the above specific preparation method, other compounds in Table 1 below can be prepared only by replacing some conditions. Specifically, the nickel compound is selected from nickel chloride or nickel bromide; the activation additive is selected from alkali metal halide; and the ligand is selected from triphenylphosphine.

TABLE-US-00001 TABLE 1 Structures of Part of Compounds of Formula (I) Compound R.sub.1 m 1 CF.sub.3 0 2 CF.sub.3 1 3 CF.sub.3 2 4 CH.sub.3 0 5 CH.sub.3 1 6 CH.sub.3 2 7 CH.sub.2CH.sub.3 0 8 CH.sub.2CH.sub.3 1 9 CH.sub.2CH.sub.2F 0 10 CH.sub.2CH.sub.2F 1 11 CH.sub.2CHF.sub.2 0 12 CH.sub.2CHF.sub.2 1 13 CH.sub.2CHF.sub.2 2 14 CH.sub.2CF.sub.3 0 15 CH.sub.2CF.sub.3 1 16 CH.sub.2CF.sub.3 2 17 CF.sub.2CHF.sub.2 0 18 CF.sub.2CHF.sub.2 1 19 CF.sub.2CHF.sub.2 2 20 CH.sub.2CH.sub.2CF.sub.3 0 21 CH.sub.2CH.sub.2CF.sub.3 1 22 CH.sub.2CH.sub.2CF.sub.3 2 23 CH.sub.2CF.sub.2CHF.sub.2 0 24 CH.sub.2CF.sub.2CHF.sub.2 1 25 CH.sub.2CF.sub.2CHF.sub.2 1 26 CH.sub.2CF.sub.2CF.sub.3 0 27 CH.sub.2CF.sub.2CF.sub.3 1 28 CH.sub.2CF.sub.2CF.sub.3 2 29 CF.sub.2CHFCF.sub.3 0 30 CF.sub.2CHFCF.sub.3 1 31 CF.sub.2CHFCF.sub.3 2 32 CH.sub.2CF.sub.2CF.sub.2CF.sub.3 0 33 CH.sub.2CF.sub.2CF.sub.2CF.sub.3 0 34 CH.sub.2CF.sub.2CF.sub.2CF.sub.3 1 35 CH.sub.2CF.sub.2CF.sub.2CF.sub.2CF.sub.3 0 36 CH.sub.2CF.sub.2CF.sub.2CF.sub.2CF.sub.3 1 37 CH.sub.2CF.sub.2CF.sub.2CF.sub.2CF.sub.3 2 38 CH.sub.2CF.sub.2CF.sub.2CF.sub.2CF.sub.2CF.sub.3 0 39 CH.sub.2CF.sub.2CF.sub.2CF.sub.2CF.sub.2CF.sub.3 1 40 CH.sub.2CF.sub.2CF.sub.2CF.sub.2CF.sub.2CF.sub.3 2 41 3, 4, 4-trifluorobut-3-en-1-yl 0 42 3, 4, 4-trifluorobut-3-en-1-yl 1