CN102516000B - Method for synthesizing aryl trifluoromethyl sulphydryl compound - Google Patents

Method for synthesizing aryl trifluoromethyl sulphydryl compound Download PDF

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CN102516000B
CN102516000B CN201110332536.XA CN201110332536A CN102516000B CN 102516000 B CN102516000 B CN 102516000B CN 201110332536 A CN201110332536 A CN 201110332536A CN 102516000 B CN102516000 B CN 102516000B
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trifluoromethyl
phenyl
boron compound
nmr
cdcl3
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CN102516000A (en
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卿凤翎
王若文
陈超
谢岩
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Shanghai Institute of Organic Chemistry of CAS
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The invention relates to a method for synthesizing an aryl trifluoromethyl sulphydryl compound. According to the invention, cheap industrial raw materials organic boric acid, elemental sulfur and fluorine-containing building block are used as raw materials to react under the catalysis of monovalent copper salt at room temperature by one kettle way so as to prepare the fluoro-substituted alkyl sulfhydryl ether compound with good yield being about 90%.

Description

A kind of method of synthesizing aryl fluoroform sulfhydryl compound
Technical field
The present invention relates to a kind of new synthetic method containing trifluoromethyl sulfhydryl compound, particularly relate to the synthetic novel method containing trifluoromethyl sulfydryl aryl compound.
Background technology
Fluoroform sulfydryl is not only strong electron-withdrawing group, and the introducing of this group can significantly improve the fat-soluble of aromatic compound, so such group is widely used as structurally-modified instrument, reaches to reduce toxic side effect, improve bioactive object.The compound with this class formation unit also extensively comes across in drug molecule, pesticide molecule (as the Toltrazuril of Beyer Co., Ltd, DE3516630,1986), bioactive molecules and organic synthesis intermediate.Containing fluoroform sulfhydryl compound, still synthesizing the important intermediate of fluorine-containing methyl sulfoxide base and sulfuryl compound----fluorine-containing methyl sulfoxide base and sulfuryl compound are also the important group that forms many pharmaceutical activity molecules.In the middle of many drug molecules and pesticide molecule, just contain above-mentioned serial functional group.The method of the compound that preparation contains Zhe Lei functional group is at present broadly divided into two kinds, fluorination method and fluorine-containing thorough method.Wherein fluorination method is first to prepare corresponding methyl chloride sulfhydryl compound intermediate, then by the method for fluoridizing, Jiang Gai functional group is converted into corresponding fluorine-containing methyl mercapto compound---and the Chinese patent (patent No. is 200610048420.2) of-for example application in 2006 prepares agricultural chemicals toltrazuril by this method; Another kind method is to carry out coupling reaction by sulfhydryl compound and containing trifluoromethyl compound, prepares corresponding trifluoromethyl sulfhydryl compound.These methods will be used harsh reaction conditions conventionally, and preparation efficiency is not too high.Professor Buchwald of Massachusetts Institute Technology has reported a kind of method of preparing aryl fluoroform sulfhydryl compound (Teverovskiy, G. of metallic palladium catalysis recently; Surry, D.S.; Buchwald, S.L.Angew.Chem.Int.Ed.2011,50,7312), can prepare efficiently this compounds, but the palladium metal catalyst of their application cost costliness, and synthesis material has also comprised fluoroform sulfydryl this costliness of silver and rare metallic compound.Importance based on this compounds, invents a kind of new novel method efficient, that low cost is prepared fluoroform sulfhydryl compound very necessary.
Summary of the invention
The object of this invention is to provide a kind ofly by the new high efficiency of copper catalysis, the preparation method of mild condition, can be widely used in preparation and there are various substituent aryl-fluoroform sulfhydryl compounds.This compounds is the important intermediate of preparing agricultural chemicals, drug molecule.This route of the present invention has reaction scheme economy, reaction yield is high, cost is low and be easy to the advantages such as suitability for industrialized production.
The invention provides a kind of synthetic method of phenyl-trifluoromethyl thioether, in organic solvent, when existing or not having additive, make phenyl boron compound, elemental sulfur and trifluoromethyl building block, under copper catalyst promotes, temperature of reaction is-10 ℃ of-100 ℃ of reactions, generate containing various substituent phenyl-trifluoromethyl thio-ether type compounds (1), the mol ratio of described phenyl boron compound, elemental sulfur, trifluoromethyl building block, copper catalyst and additive is 1: (0.1-50): (0.2-50): (0.005-2): (0-10), reaction formula is:
Wherein said X is H, Br, I, Cl, NO 2, NH 2, NR 2, OH, OR, SR, SO 2r etc., X is upper monosubstituted, two replacement or trisubstituted groups; R is the alkyl of C1-C6;
R 1for the benzo base (alkoxyl group that the substituting group on benzo base is C1-C6) of the thiazolinyl of H, phenyl, C2-C4, benzoyl, methylsulfonyl, amine acyl group, replacement, the phenoxy group (alkoxyl group that substituting group is C1-C6 or nitro) replacing, alkyl or the acyl group of C1-C6, R 1for upper monosubstituted, two replacement or trisubstituted groups, and when Z1, Z2 are CH, total replacement number of R1 and X is no more than 5; When Z1, Z2 are N, total replacement number of R1 and X is no more than 3, and when Z1, Z2 are CH and N, total replacement number of R1 and X is no more than 4;
Z1, Z2 are identical or different group, are selected from CH or N, are preferably CH;
BY can be B (OH) 2, BF 4, or boric acid ester group;
R 3can be trimethyl silicon based (Me 3si) or the silica-based (Et of triethyl 3si).
Recommend:
Copper catalyst is monovalence copper catalyst, and cuprous salt is CuCN preferably, CuSCN, and CuI or CuBr, its consumption is the 0.001-0.5 equivalent of phenyl boron compound, optimum amount is the 0.005-0.2 equivalent of phenyl boron compound; Copper catalyst be mantoquita be combined by coordinate bond with nitrogenous organic ligand mixture, the molar ratio of copper and nitrogenous organic ligand is 0.1-10, optimum molar ratio is 0.5-2; Described nitrogenous organic ligand is 10-phenanthroline, 2, and 2 '-bipyridine, EDTA etc.; By CuCN, CuI or CuSCN and 1,10-phenanthroline, the molar ratio with 0.5-2 prepares copper catalyst; Temperature of reaction is 0 ℃-50 ℃, and optimal reaction temperature is room temperature; Additive is silver carbonate or silver carbonate and potassiumphosphate, and consumption is the 0.5-10 equivalent of phenyl boron compound, and optimum amount is 2 equivalents of phenyl boron compound; Phenyl boron compound is the bromo-phenyl-boron dihydroxide of 4-, the iodo-phenyl-boron dihydroxide of 4-or 4-(2-methyl-4-nitro) benzene oxygen-phenyl-boron dihydroxide.The preferred DMF of described organic solvent or dimethyl sulfoxide (DMSO).
By present method, by the efficient synthetic phenyl trifluoromethyl thioether of this boric acid, be the key intermediate of preparing agricultural chemicals toltrazuril
The present invention also provides a kind of synthetic method of aryl-trifluoromethyl thioether, elemental sulfur, aryl or heteroaryl boron compound, trifluoromethyl building block are contacted in reactor, under the promotion of copper catalyst and additive, temperature of reaction is-10 ℃-100 ℃ carries out, and generates aryl-trifluoromethyl thio-ether type compounds.
Wherein aryl or heteroaryl Ar are naphthalene, pyridine, thiophene, furans, oxazole, thiazole etc., R 3as previously mentioned, the mol ratio of described aryl boron compound, elemental sulfur, trifluoromethyl building block, copper catalyst and additive is 1: (0.1-50): (0.2-50): (0.005-2): (0-10).
Aryl-fluoroform sulfhydryl compound involved in the present invention can have following general structure: Ar-SCF 3, wherein Ar is phenyl, naphthalene, pyridine, furans, thiophene, oxazole, thiazole etc.Because used raw material is organic boronic, there is in the method for the invention high reaction activity, and the reaction conditions of gentleness of the present invention, therefore can prepare and there are various substituent aryl-fluoroform sulfhydryl compounds by method of the present invention.
The heterogeneous ring compound that recommendation relates to has following general structure:
In its formula of 1, substituent X is Br, I, Cl, NO 2, NH 2, NR 2, OH, OR, SR, SO 2r etc., quantity is 0-3; R 1for having alkyl, the acyl group of various substituent C1-C6, quantity is 0-3; BR 2for aryl boric acid, aryl-boric acid ester, and aryl tetrafluoride boron salt; R3 is trimethyl silicon based (Me 3si), the silica-based (Et of triethyl 3si).
Preferably the present invention is achieved in that (be that market is commonly called as sulphur powder, molecular formula is for can be written as S with inexpensive industrial raw material organoboron compound (1 equivalent), elemental sulfur for the method 8or S, 0.5-20 equivalent) be raw material with containing trifluoromethyl building block-----trifluoromethyl trimethyl silane or trifluoromethyl triethyl silicane (0.5-30 equivalent), under copper catalyst (0.001-0.5 equivalent) catalysis of catalytic amount with the promotion of additive under, in the 1-40 hour good yield with 90% left and right of 0-50 ℃ of reaction, prepare aryl-fluoroform sulfhydryl compound.
Copper catalyst involved in the present invention by cuprous salt (CuX) as Cul, CuBr, CuCl, CuOTf, CuCN, CuSCN etc. with organic ligand as 10-phenanthroline, 2,2 '-bipyridine, it is better that the coordination such as EDTA forms effect; Wherein use CuSCN and 1,10-phenanthroline (1,10-phenanthroline) as catalyzer, can play best catalytic effect.Only use cuprous salt or use cupric or zerovalent copper also catalyzed reaction to carry out----in reaction process, the copper of different valence state can transform mutually, and in the absence of organic ligand, reaction also can be carried out, but effect is poor.
In reaction, add oxygenant if silver carbonate and alkali are if potassiumphosphate etc. is as additive, can effectively promote the carrying out of reaction, improve productive rate, but these additives are to reaction non-key.
In application trifluoromethyl building block, attempted two kinds of trifluoromethyl trimethyl silane or trifluoromethyl triethyl silicanes, effect is more or less the same, but due to trifluoromethyl trimethyl silane cost but, therefore in embodiment, substantially adopt this building block.
In method of the present invention, for example aryl boric acid, aryl-boric acid ester and aryl tetrafluoride boron salt effect are more or less the same to use various aryl boron compounds.
Different with traditional preparation method, traditional preparation method is raw material with the organic compound containing element sulphur, by coupling reaction, prepares this compounds.Present method directly utilizes elemental sulfur as sulphur source, by three component reaction, and coupled aryl-fluoroform sulfhydryl compound that obtains.For this one pot reaction, the course that may experience is as follows, and first monovalence copper react with elemental sulfur, forms a kind of copper salt containing disulfide linkage, and this mantoquita and aryl boron compound and the complexing of trifluoromethyl silica reagent, through the coupled compound that obtains design.
Concrete embodiment
By following embodiment, will contribute to understand the present invention, but not limit content of the present invention.
Embodiment 1: phenyl-boron dihydroxide, elemental sulfur and the trifluoromethyl trimethyl silane coupling reaction under the catalysis of monovalence copper.
With N, dinethylformamide (5ml) is as solvent, add phenyl-boron dihydroxide (0.2), elemental sulfur (0.6mmol) and trifluoromethyl trimethyl silane (1.0-mmol), at any monovalence copper catalyst, stir at ambient temperature 24 hours under as cuprous iodide (0.02mmol) katalysis.By 19f NMR follows the tracks of reaction, until reaction is carried out completely.Except after desolventizing, column chromatography or distillation obtain corresponding aryl trifluoromethyl thioether.Productive rate is 45%.Related data is as follows: 1h NMR (300MHz, CDCl3,293K, TMS): δ ppm7.35-7.39 (m, 4H), 7.23 (t, J=8.4Hz, 1H). 19f NMR (282MHz, CDCl3): δ ppm-42.81 (s, 3F). 13c NMR (100.7MHz, CDCl3,293K, TMS): δ ppm166.04,129.53 (d, J=0.8Hz), 128.93,125.40,36.46.IR (ATR): vmax 2955.49,1436.91,1284.86,1160.71,1017.51,764.68,693.19cm -1.MS (EI): m/z (%) 178.
Embodiment 2: phenyl-boron dihydroxide, elemental sulfur and the trifluoromethyl trimethyl silane coupling reaction under monovalence copper and organic ligand catalysis.
With N, dinethylformamide (5ml) is as solvent, add phenyl-boron dihydroxide (0.2mmol), elemental sulfur (0.6mmol), (this additive does not cause productive rate to reduce to additive potassiumphosphate (0.4mmol) with silver carbonate (0.4mmol), oxygenant and the alkali of using other instead also cause productive rate to have certain reduction), and trifluoromethyl trimethyl silane (1.0-mmol) is 1, 10-phenanthroline (phen, under the catalysis of catalyzer 0.04mmol) forming with CuSCN (0.02mmol), (parallel test proves in 25 ℃, temperature of reaction productive rate between 0-50 ℃ changes little, temperature of reaction exceeds this scope, leading productive rate reduces) stir 24 hours ( 19f NMR follows the tracks of and finds to have suitable product to generate after 1 hour).By 19f NMR follows the tracks of reaction, until reaction is carried out completely.Except after desolventizing, column chromatography or distillation obtain corresponding aryl trifluoromethyl thioether.Productive rate is 90%, and this condition is optimal condition of the present invention.
Embodiment 3: phenyl tetrafluoride boron, elemental sulfur and the trifluoromethyl triethyl silicane coupling reaction under monovalence copper and organic ligand catalysis.
With N, dinethylformamide (5ml) is as solvent, add phenyl tetrafluoride boron (0.2mmol), elemental sulfur (0.6mmol), potassiumphosphate (0.4mmol) and silver carbonate (0.4mmol) and trifluoromethyl triethyl silicane (1.0-mmol) 1,10-phenanthroline (phen, under the catalysis of catalyzer 0.04mmol) forming with CuSCN (0.02mmol), under room temperature condition, stir 24 hours.Except after desolventizing, column chromatography or distillation obtain corresponding aryl trifluoromethyl thioether.Productive rate is 89%, found through experiments, and phenyl boronate, in this reaction, also has similar reactive behavior.
Embodiment 4: under optimum reaction condition, have phenyl-boron dihydroxide and elemental sulfur and the coupling reaction of trifluoromethyl trimethyl silane under copper catalysis of different substituents.
With N, dinethylformamide (5ml) is as solvent, add the phenyl-boron dihydroxide (0.2mmol), elemental sulfur (0.6mmol), additive potassiumphosphate (0.4mmol) with different substituents and silver carbonate (0.4mmol) and trifluoromethyl trimethyl silane (1.0-mmol) 1,10-phenanthroline (phen, under the catalysis of catalyzer 0.04mmol) forming with CuSCN (0.02mmol), in 25 ℃, stir 24 hours.By 19f NMR follows the tracks of reaction, until reaction is carried out completely.Except after desolventizing, column chromatography or distillation obtain corresponding aryl trifluoromethyl thioether.Productive rate is 70-92%.Related compound data are as follows:
3-fluoroform sulfydryl biphenyl
1h NMR (300MHz, CDCl3,293K, TMS): δ ppm 7.89 (s, 1H), 7.72 (d, J=7.5Hz, 1H), 7.66-7.58 (m, 3H), 7.53-7.38 (m, 4H). 19f NMR (282MHz, CDCl3): δ ppm-42.95 (s, 3F). 13c NMR (100.7MHz, CDCl3,293K, TMS): δ ppm142.75,139.59,134.95 (d, J=0.8Hz), 134.86 (d, J=0.8Hz), 129.81,129.65 (q, J=308.7Hz), 129.56,128.97,127.99,127.17,124.90 (q, J=2.1Hz) .IR (ATR): v max3062.83,3032.69,1590.50,1469.50,1401.89,1117.69,1098.03,795.59,756.79,696.89cm -1.MS (EI): m/z (%) 254 (100) .HRMS:Calculated for (calculated value) C 13h 9f 3s:254.0377; Found (measured value): 254.0376.
1-vinyl-4-fluoroform sulfydryl benzene
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.61(d，J＝8.1Hz，2H)，7.44(d，J＝8.4Hz，2H)，6.72(dd，J＝10.8Hz，J＝17.4Hz，1H)，5.83(d，J＝17.1Hz，1H)，5.37(d，J＝11.1Hz，1H). 19F?NMR(282MHz，CDCl3)：δppm-43.27(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?140.09，136.50(d，J＝0.9Hz)，135.59，129.54(q，J＝308.7Hz)，127.12，123.26(q，J＝2.1Hz)，116.35.IR(ATR)：v max?2926.90，1396.84，1160.00，1118.30，1085.79，918.02，840.08cm -1.MS(EI)：m/z(％)204，135(100).HRMS：(Calculated?for)C 9H 7F 3S：204.0221；(Found)：204.0222.
3,4,5-trichlorophenyl trifluoromethyl thioether
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.90(s，2H). 19F?NMR(282MHz，CDCl3)：δppm-43.27(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?137.3，136.6，135.08，129.7，127.58.IR(ATR)：v max?2929.80，1474.36，1387.95，1211.72，1118.98，1083.70，1067.55，1010.57，819.08，756.25，cm -1.MS(EI)：m/z(％)279.
The chloro-phenyl trifluoromethyl thioether of the bromo-6-of 3,4-bis-
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?8.10(s，1H)，7.90(s，1H). 19F?NMR(282MHz，CDCl3)：δppm-42.27(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?137.2，136.1，132.78，129.0，128.5，124.2，123.7.IR(ATR)：v max?2929.80，1474.36，1387.95，1211.72，1118.98，1067.55，819.08，756.25，cm -1.MS(EI)：m/z(％)367.
4-bromophenyl trifluoromethyl thioether
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.56(d，J＝8.7Hz，2H)，7.51(d，J＝8.7Hz，2H). 19F?NMR(282MHz，CDCl3)：δppm-43.17(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?137.72(d，J＝1.0Hz)，132.78，129.18(q，J＝309.1Hz)，125.98，123.39(q，J＝2.3Hz).IR(ATR)：v max?2929.80，1474.36，1387.95，1211.72，1118.98，1083.70，1067.55，1010.57，819.08，756.25，732.26cm -1.MS(EI)：m/z(％)256，258(100).HRMS：Calculated?for?C 7H 4BrF 3S：255.9169；Found：255.9173.
The iodo-phenyl trifluoromethyl thioether of 3,6-bis-
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?8.10(s，1H)，7.55(d，1H)，7.33(1H)，7.31(d，1H). 19F?NMR(282MHz，CDCl3)：δppm-42.57(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?146.1，139.4，137.1，135.7，135.6，93.4，90.6.IR(ATR)：v max?2928.80，1475.36，139.95，1231.72，1108.98，1060.55，811.08，750.25，cm -1.MS(EI)：m/z(％)429.
4-nitro-phenyl trifluoromethyl thioether
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.86(d，J＝8.7Hz，2H)，7.81(d，J＝8.7Hz，2H). 19F?NMR(282MHz，CDCl3)：δppm-43.27(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?139.72(d，J＝1.0Hz)，135.78，133.18(q，J＝309.1Hz)，129.98，126.39(q，J＝2.3Hz).IR(ATR)：v max?2927.80，1476.36，1380.95，1202.72，1111.98，1080.70，1065.55，1005.57，816.08，753.25，730.26cm -1.MS(EI)：m/z(％)223.
3-amido-4-(N, N dimethylamine base)-phenyl trifluoromethyl thioether
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.07(1H)，7.04(1H)，6.41(1H)，3.06(6H). 19F?NMR(282MHz，CDCl3)：δppm-43.07(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm134.7，134.0，126.7，122.3，115.3，114.1，46.1.MS(EI)：m/z(％)236.
4-benzoylphenyl fluoroform thioether
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.84-7.74(m，6H)，7.61(t，J＝7.8Hz，1H)，7.49(t，J＝7.5Hz，2H). 19F?NMR(282MHz，CDCl3)：δppm-42.20(s，3F).
13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?195.56，139.44，136.78，135.52(d，J＝0.9Hz)，132.98，130.67，130.05，129.33(q，J＝309.1Hz)，129.12(q，J＝2.3Hz)，128.49.IR(ATR)：v max?3066.71，1658.89，1569.80，1448.31，1396.31，1306.29，1284.32，1125.74，1082.45，1015.57，925.98，847.67，731.64，697.08cm -1.MS(EI)：m/z(％)282，105(100).HRMS：Calculated?for?C 14H 9F 3OS：282.0326；Found：282.0330.
4-methylsulfonyl phenyl trifluoromethanesulfonate dimethyl sulfide
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.99(d，J＝8.4Hz，2H)，7.84(d，J＝8.4Hz，2H)，3.08(s，3H). 19F?NMR(282MHz，CDCl3)：δppm-42.17(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?142.79，136.32，131.63(q，J＝2.2Hz)，129.20(q，J＝309.2Hz)，128.47，44.46.IR(ATR)：v max3018.59，2927.31，2257.65，1919.70，1583.41，1391.74，1319.48，1111.11，1082.28，969.94，776.24，737.25cm -1.MS(EI)：m/z(％)256(100).HRMS：Calculated?for?C 8H 7F 3O 2S 2：255.9840；Found：255.9838.
M-fluoroform sulfydryl benzamide
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?8.11(s，1H)，7.95(d，J＝7.5Hz，1H)，7.82(d，J＝7.2Hz，1H)，7.52(t，J＝7.5Hz，1H)，6.33(br，2H). 19F?NMR(282MHz，CDCl3)：δppm-42.80(s，3F). 13C?NMR(100.7MHz，acetone-d6，293K)：δppm?166.59，138.85，136.19，135.32，130.34，129.92，129.84(q，J＝307.1Hz)，124.16(d，J＝2.2Hz).IR(ATR)：v max?3368.86，3192.94，2476.81，2395.02，1669.45，1639.38，1567.16，1401.07，1130.66，1108.49cm -1.MS(EI)：m/z(％)221，205(100).HRMS：Calculated?for?C 8H 6F 3NOS：221.0122；Found：221.0124.
2-methoxyl group-6-fluoroform mercaptonaphthalene (2g)
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?8.11(s，1H)，7.75(d，J＝9.0Hz，2H)，7.61(d，J＝7.5Hz，1H)，7.22(t，J＝9.6Hz，1H)，7.14(s，1H)，3.93(s，3H). 19F?NMR(282MHz，CDCl3)：δppm-43.37(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?158.22，135.97(d，J＝0.9Hz)，134.49，131.62，128.77(q，J＝309.1Hz)，128.72，127.92，126.95，118.95，117.54(q，J＝2.0Hz)，104.61，54.39.IR(ATR)：v max?2961.32，2938.61，1627.17，1498.92，1389.94，1265.35，1214.42，1111.48，1031.79，852.61，659.84cm-1.MS(EI)：m/z(％)258，189(100).HRMS：Calculated?for?C 12H 9?F 3OS：258.0326；Found：258.0325.
(4-(2-methyl-4-nitrophenoxy) phenyl trifluoromethyl thioether
1H?NMR(300MHz，CDCl 3)δ8.15(d，J＝2.7Hz，1H)，8.01(dd，J＝8.6，2.8Hz，1H)，7.65(d，J＝8.5Hz，2H)，7.15(m，2H)，6.91(d，J＝8.6Hz，1H)，2.35(s，3H). 13C?NMR(100.7MHz，CDCl 3)δ160.19(s)，159.02(s)，144.34(s)，139.34(s)，131.42(s)，130.16(q，J＝308.2Hz)，127.68(s)，123.89(s)，120.33(s)，119.99(dd，J＝4.4，2.2Hz)，118.73(s)，16.97(s).19F?NMR(471MHz，CDCl3)δ-43.48(s).IR(film)v max?3092.96，2928.72，2856.16，2270.72，2023.09，1903.95，1617.82，1581.03，1522.70，1485.23，1345.34，1247.74，1213.91，1117.85，1087.46，1013.59，931.93，900.25，856.71，830.53，803.93，747.36，519.60cm -1.Anal.Calcd.For?C 14H 10F 3NO 3S：C，51.06；H，3.06.Found：C，51.20；H，3.02。
4-itrile group-phenyl trifluoromethanesulfonate dimethyl sulfide
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.77(d，J＝7.8Hz，2H)，7.72(d，J＝8.4Hz，2H). 19F?NMR(282MHz，CDCl3)：δppm-41.94(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?134.96(d，J＝1.3Hz)，131.91，129.56，128.02(q，J＝309.5Hz)，116.59，113.66.IR(ATR)：vmax?2925.49，2233.83，1487.36，1161.65，1115.37，1081.86，1018.40，835.21，757.48，545.87cm -1.MS(EI)：m/z(％)203，134(100).HRMS：Calculated?for?C8H4F3NS：203.0017；Found：203.0016.
4-phenoxy group-phenyl trifluoromethanesulfonate dimethyl sulfide
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.58(d，J＝8.4Hz，2H)，7.38(t，J＝7.5Hz，2H)，7.20(t，J＝7.5Hz，1H)，7.07δ6.94(m，4H). 19F?NMR(282MHz，CDCl3)：δppm-43.93(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?159.42，154.61，137.35(d，J＝0.9Hz)，129.07，128.59(q，J＝309.1Hz)，123.57，119.09，117.62，116.24(q，J＝2.1Hz).IR(ATR)：v max1582.45，1488.21，1280.61，1251.37，1103.50，1083.90，869.58，835.45，755.95，692.87cm -1.MS(EI)：m/z(％)270(100).HRMS：Calculated?for?C 13H 9F 3OS：270.0326；Found：270.0330.
4-benzyloxy-phenyl-trifluoromethyl thioether
1H?NMR(300MHz，CDCl3，293K，TMS)：δ7.46(d，J＝9.0Hz，2H)，7.31-7.23(m，5H)，6.88(m，J＝9.0Hz，2H)，4.95(s，2H). 19F?NMR(282MHz，CDCl3)δ-44.19(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δ160.08，137.35，135.24，128.70(q，J＝308.7Hz)，127.75，127.30，126.53，114.89，114.17(q，J＝2.1Hz)，69.20.IR(ATR)：v max?3035.20，1593.32，1493.49，1250.30，1117.95，1087.57，1007.80，829.56，736.07，697.34cm -1.MS(EI)：m/z(％)284，91(100).HRMS：Calculated?for?C 14H 11F 3OS：284.0483；Found：284.0487
1-tert-Butyl-4-[(trifluoromethyl)thio]benzene(2f)
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.57(d，J＝8.1Hz，2H)，7.43(d，J＝8.4Hz，2H)，1.33(s，9H). 19F?NMR(282MHz，CDCl3)：δppm-43.45(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?153.36，135.12(d，J＝1.9Hz)，128.68(q，J＝308.3Hz)，125.57，119.86(d，J＝2.1Hz)，33.85，30.13.IR(ATR)：v max?2966.26，2922.98，1489.28，1156.05，1127.51，1103.83，831.42，755.75，567.35cm -1.MS(EI)：m/z(％)234，219(100).H?RMS：Calculated?for?C 11H 13F 3S：234.0690；Found：234.0692.
3,4,5-trimethoxy-phenyl-trifluoromethyl thioether
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?6.87(s，2H)，3.88(s，9H). 19F?NMR(282MHz，CDCl3)：δppm-43.48(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?153.40，140.49，129.57(q，J＝309.1Hz)，118.44(q，J＝2.1Hz)，113.62(d，J＝0.8Hz)，60.88，56.29.IR(ATR)：v max?2940.45，2834.79，1582.97，1499.76，1463.47，1407.99，1310.79，1235.17，1126.75，1005.00，878.17，832.11.622.60cm -1.MS(EI)：m/z(％)268(100).HRMS：Calculated?for?C 10H 11F 3O 3S：268.0381；Found：268.0384.
3-(N-2-ethylamino--propyl group)-phenyl-trifluoromethyl thioether
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.44(d，1H)，7.30(d，1H)，7.21(1H)，7.05(1H)，3.18(1H)2.79(2H)，2.59(2H)，1.12(3H)，1.02(3H). 19F?NMR(282MHz，CDCl3)：δppm-42.45(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?138.2，136.6，136.5，129.0，126.6，124.5，123.2，56.4，44.3，41.9，21.1，15.9.IR(ATR)：v max?3216，2962.26，1485.28，1152.05，1125.51，831.42，cm -1.MS(EI)：m/z(％)263.
Embodiment 5: under optimal conditions, and aryl-heterocyclic boric acid, elemental sulfur and the coupling reaction of trifluoromethyl triethyl silicane under copper catalysis.
With N, dinethylformamide (5ml) is as solvent, add the aryl-heterocyclic boric acid (0.2mmol), elemental sulfur (0.6mmol), additive potassiumphosphate (0.4mmol) with different structure and silver carbonate (0.4mmol) and trifluoromethyl triethyl silicane (1.0-mmol) 1,10-phenanthroline (phen, under the catalysis of catalyzer 0.04mmol) forming with Cul (0.02mmol), in 25 ℃, stir 24 hours.By 19f NMR follows the tracks of reaction, until reaction is carried out completely.Except after desolventizing, column chromatography or distillation obtain corresponding aryl trifluoromethyl thioether.Productive rate is 68-88%.Related compound data are as follows:
2-fluoroform mercaptopyridine 4a:
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?8.95(d，J＝2.1Hz，1H)，8.14(d，J＝7.8Hz，1H)，8.06(d，J＝8.1Hz，1H)，7.86(q，J＝3.6Hz，1H). 19F?NMR(282MHz，CDCl3)：δppm-41.80(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?159.91，148.50，136.32，131.63(q，J＝308.7Hz)，121.80，119.35.IR(film)：v max?3038.86，1626.58，1565.90，1366.42，1143.05，1131.95，1113.51，1081.70，956.02，648.17cm -1.MS(EI)：m/z(％)179(100).HRMS：Calculated?for?C 6H 4?F 3NS：179.0017；Found：179.0020.
2-fluoroform mercaptopyrimidine 4b:
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?8.93(d，J＝5.1Hz，2H)，7.53(t，J＝4.8Hz，1H). 19F?NMR(282MHz，CDCl3)：δppm-41.27(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?171.92，156.86，132.63(q，J＝308.2Hz)，116.25.IR(film)：v max?3078.89，1642.20，1539.36，1355.54，1150.44，1131.95，1113.51，956.02，745.17cm -1.MS(EI)：m/z(％)180(100).HRMS：Calculated?for?C 5H 3?F 3N 2S：179.9969；Found：179.9971.
Compound 4c:
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?8.31(q，J＝8.4Hz，1H)，7.71(t，J＝3.0Hz，3H)，7.47(q，J＝0.6Hz，4H)，4.24(t，J＝6.0Hz，1H). 19F?NMR(282MHz，CDCl3)：δppm-42.08(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?145.19，137.74，133.62，131.63(q，J＝308.2Hz)，129.25，128.79，127.54，126.43，120.35，114.49.MS(EI)：m/z(％)294(100).HRMS：Calculated?for?C 14H 9F 3N 2S：294.0439；Found：294.0436.
2-nitro-5-fluoroform mercapto-thiophene 6a:
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.88(q，J＝1.2Hz，1H)，7.41(q，J＝0.9Hz，1H). 19F?NMR(282MHz，CDCl3)：δppm-43.37(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?154.19，146.72，132.93(q，J＝309.2Hz)，130.10，129.61.MS(EI)：m/z(％)229(100).HRMS：Calculated?for?C 5H 2?F 3NO 2S 2：228.9479；Found：228.9475.
2-fluoroform mercaptobenzothiazole 6b:
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?8.19(d，J＝8.4Hz，1H)，7.96(d，J＝8.1Hz，1H)，7.63-7.52(m，2H). 19F?NMR(282MHz，CDCl3)：δppm-42.11(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?164.72，153.55，135.19，130.63(q，J＝308.2Hz)，125.37，124.93，121.66，1,19.89.IR(film)：v max?1632.74，1490.35，1253.29，1112.47，1014.13，853.90，612.17cm -1.MS(EI)：m/z(％)235(100).HRMS：Calculated?for?C 8H 4?F 3NS 2：234.9737；Found：234.9735.
2-methoxyl group-5-fluoroform sulfydryl furans 8a
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.88(q，J＝1.2Hz，1H)，7.41(q，J＝0.9Hz，1H).4.32(s). 19F?NMR(282MHz，CDCl3)：δppm-42.98(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?166.56，139.04，133.10(q，J＝308.2Hz)，116.29，89.97，59.66.MS(EI)：m/z(％)198(100).HRMS：Calculated?for?C 6H 5?F 3O 2S：197.9962；Found：197.9965.
2-fluoroform mercaptobenzoxazole 8b
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?8.19(d，J＝8.4Hz，1H)，7.96(d，J＝8.1Hz，1H)，7.63-7.52(m，2H). 19F?NMR(282MHz，CDCl3)：δppm-42.36(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?164.80，155.55，136.19，129.63(q，J＝308.2Hz)，125.30，124.91，120.66，119.80.IR(film)：v max?1531.97，1449.90，1253.30，1112.40，1014.83，853.98，610.17cm -1.MS(EI)：m/z(％)219(100).HRMS：Calculated?for?C 8H 4?F 3NOS：218.9966；Found：218.9967.
2-methoxycarbonyl-5-fluoroform sulfydryl furans 8c
1H?NMR(300MHz，CDCl3，293K，TMS)：δppm?7.88(q，J＝1.2Hz，1H)，7.41(q，J＝0.9Hz，1H).4.21(s). 19F?NMR(282MHz，CDCl3)：δppm-41.12(s，3F). 13C?NMR(100.7MHz，CDCl3，293K，TMS)：δppm?184.36，166.56，139.04，133.10(q，J＝308.2Hz)，116.29，，96.65，59.66.MS(EI)：m/z(％)226(100).HRMS：Calculated?for?C 7H 5?F 3O 3S：225.9911；Found：225.9915.

Claims (10)

1. the synthetic method of aryl-trifluoromethyl thioether, it is characterized in that: in organic solvent, when existing or not having additive, make phenyl boron compound or pyridyl boron compound or pyrimidyl boron compound, elemental sulfur and trifluoromethyl building block, under copper catalyst promotes, temperature of reaction is-10 ℃ of-100 ℃ of reactions, generate aryl-trifluoromethyl thio-ether type compounds (1), described phenyl boron compound or pyridyl boron compound or pyrimidyl boron compound, elemental sulfur, trifluoromethyl building block, the mol ratio of copper catalyst and additive is 1:(0.1-50): (0.2-50): (0.005-2): (0-10), reaction formula is:
Wherein said X is H, Br, I, Cl, NO 2, NH 2, NR 2, OH, OR, SR or SO 2r; X is upper monosubstituted, two replacement or trisubstituted groups; R is the alkyl of C1-C6;
R 1the benzo base replacing for the alkoxyl group of the thiazolinyl of H, phenyl, C2-C4, benzoyl, methylsulfonyl, amine acyl group, C1-C6 is, the phenoxy group that the alkoxyl group of C1-C6 or nitro replace, alkyl or the acyl group of C1-C6, R 1for upper monosubstituted, two replacement or trisubstituted groups; And when Z1, Z2 are CH, total replacement number of R1 and X is no more than 5; When Z1, Z2 are N, total replacement number of R1 and X is no more than 3; When Z1, Z2 are CH and N, total replacement number of R1 and X is no more than 4;
Z1, Z2 are identical or different group, are selected from CH or N;
BY can be B (OH) 2, BF 4, or boric acid ester group;
R 3can be trimethyl silicon based or triethyl is silica-based;
Described copper catalyst is the mixture that cuprous salt catalyzer or mantoquita are combined by coordinate bond with nitrogenous organic ligand.
2. synthetic method as claimed in claim 1, is characterized in that described cuprous salt catalyzer is CuCN, CuSCN, and CuI or CuBr, its consumption is the 0.005-0.5 equivalent of phenyl boron compound or pyridyl boron compound or pyrimidyl boron compound.
3. synthetic method as claimed in claim 1, it is characterized in that described copper catalyst be mantoquita be combined by coordinate bond with nitrogenous organic ligand mixture, the molar ratio of mantoquita and nitrogenous organic ligand is 0.1-10.
4. synthetic method as claimed in claim 3, is characterized in that described nitrogenous organic ligand is 10-phenanthroline, 2, and 2 '-bipyridine or EDTA.
5. synthetic method as claimed in claim 4, is characterized in that the molar ratio with 0.5-2 prepares described copper catalyst by CuCN, CuI or CuSCN and 1,10-phenanthroline.
6. synthetic method as claimed in claim 4, wherein temperature of reaction is 0 ℃-50 ℃.
7. synthetic method as claimed in claim 4, is characterized in that described additive is silver carbonate or silver carbonate and potassiumphosphate, and consumption is the 0.5-10 equivalent of phenyl boron compound or pyridyl boron compound or pyrimidyl boron compound.
8. synthetic method as claimed in claim 1, it is characterized in that described phenyl boron compound is the bromo-phenyl-boron dihydroxide of 4-, the iodo-phenyl-boron dihydroxide of 4-or 4-(2-methyl-4-nitro) benzene oxygen-phenyl-boron dihydroxide is the key intermediate of preparing agricultural chemicals toltrazuril by present method by the efficient synthetic phenyl trifluoromethyl thioether of this boric acid.
9. synthetic method as claimed in claim 1, is characterized in that described organic solvent is DMF or dimethyl sulfoxide (DMSO).
10. the synthetic method of aryl-trifluoromethyl thioether, its feature is being that described elemental sulfur, aryl boron compound, trifluoromethyl building block contacts in reactor, under the promotion of copper catalyst and additive, temperature of reaction is-10 ℃-100 ℃ carries out, and generates aryl-trifluoromethyl thio-ether type compounds;
Wherein aryl Ar is naphthalene, pyridine, thiophene, furans, oxazole, thiazole; Described copper catalyst is CuI; R 3as claimed in claim 1, the mol ratio of described aryl boron compound, elemental sulfur, trifluoromethyl building block, copper catalyst and additive is 1:(0.1-50): (0.2-50): (0.005-2): (0-10).
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