CN103787802A - Aryl alkyl thioether compounds and synthesis method thereof - Google Patents

Aryl alkyl thioether compounds and synthesis method thereof Download PDF

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CN103787802A
CN103787802A CN201410048015.5A CN201410048015A CN103787802A CN 103787802 A CN103787802 A CN 103787802A CN 201410048015 A CN201410048015 A CN 201410048015A CN 103787802 A CN103787802 A CN 103787802A
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CN103787802B (en
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姜雪峰
李一鸣
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East China Normal University
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Abstract

The invention discloses aryl alkyl thioether compounds and a synthesis method thereof. The synthesis method comprises the steps: in a reaction solvent, with an arylamine derivative and halogenated hydrocarbon as reaction raw materials, and Na2S2O3 as a vulcanization reagent, in the presence of a copper reagent catalyst, and reacting to obtain the aryl alkyl thioether compounds. According to the synthesis method disclosed by the invention, raw materials are easy to obtain and low in price, the reaction operation is simple, the reaction conditions are mild, the yield is higher, the tolerance of a functional group is excellent, later-phase modification of compounds of medicines, sugars, amino acids and the like is successfully realized, and an efficient method for constructing a carbon-sulfur bond is provided for researches of medicinal chemistry and biology orthogonal chemistry.

Description

One class arylalkyl sulfide compound and synthetic method thereof
Technical field
The invention belongs to organic compound process application technical field, be specifically related to class arylalkyl sulfide compound and a synthetic method thereof.
Background technology
Arylalkyl sulfide compound is a kind of very important compound, it is extensively present in various kinds of drug shown below and comprises in Sulfide-containing Hindered structure medicament molecule, material and food, therefore, build C-S key from some simple in structure, commercial compounds that can obtain in a large number and seem particularly important.
Figure BDA0000465014200000011
The traditional method of synthesizing aryl alkyl thioether compound is mainly by mercaptan or thiophenol compounds and prepares.These class methods, the organosulfur class that uses easily oxidized, metal catalytic is had to poisoning effect; Raw material taste is overweight, and environment and human body are all had to injury in various degree; Raw material is comparatively expensive, and complex substrate needs pre-prepared; Many deficiencies have restricted the profound level application of these class methods in technical study and pharmaceutical chemistry research field above.
" modification of drug molecule later stage " has been subject to the extensive concern of scientists as a kind of novel research method in pharmaceutical chemistry field.So far, effectively " sulfuration of drug molecule later stage " method has not yet to see report.Therefore the method that, develops a kind of brand-new " sulfuration of complex system later stage " just seems and is even more important.The inventor commonly uses arylamine class formation ubiquity in medicine, pesticide molecule below investigation is found at present, and Given this, the new and effective vulcanization reaction that builds aromatic amine compounds becomes the vertical topic foundation of the present invention and technical problem to be solved.
Figure BDA0000465014200000021
Summary of the invention
The present invention has overcome the shortcomings of traditional vulcanization reaction, realizes innovatively a kind of method of efficient structure arylalkyl sulfide compound.The present invention uses cheap α-benzoinoxime catalyzer, take aromatic amine compounds, alkyl halide as raw material, with Na 2s 2o 3for sulfuration reagent, using alcohol and water as reaction solvent, effectively realize corresponding conversion, prepare arylalkyl sulfide compound as shown in the formula (II).
Wherein, described reaction process is as shown in following reaction formula.
Figure BDA0000465014200000022
In above reaction formula, Ar is phenyl ring, heterocycle, substituted benzene ring or substituted heterocycle; R is straight chained alkyl, branched paraffin or contains aromatic yl paraffin.X is I, Br or Cl; R ' is straight chained alkyl, branched paraffin or contains aromatic yl paraffin.Preferably, Ar is phenyl ring, heterocycle, substituted benzene ring or substituted heterocycle.R is straight chained alkyl, containing aromatic yl paraffin.X is Br, Cl.R ' is branched paraffin.In the present invention, Ar, R, X, R ' include but are not limited to above-mentioned group.
As above reaction formula, the present invention utilizes the aromatic amine compound shown in formula (I), and halogenated alkane is as starting raw material, with Na 2s 2o 3as sulfuration reagent, under the effect of α-benzoinoxime catalyzer, in reaction solvent, react synthetic arylalkyl sulfide compound as shown in the formula (II).
In the present invention, described starting raw material aromatic amine compounds (substrate 1) and sulfuration reagent N a as shown in the formula (I) 2s 2o 3usage ratio be 1:1-1:15.Preferably, both usage ratio are 1:7.
In the present invention, described starting raw material aromatic amine compounds and halogenide halogenated alkane (substrate 2) usage ratio is as shown in the formula (I) 1:1-1:15.Preferably, both usage ratio are 1:7.
In the present invention, with Na 2s 2o 3for sulfuration reagent.
In the present invention, described copper catalyst is CuSO 4, CuSO 45H 2o, Cu (OAc) 2, Cu (NO 3) 2, Cu (TFA) 2, Cu (OTf) 2, CuCl 2, CuBr 2, Cu (acac) 2, CuO, CuOAc, CuI, CuBr, CuCl, CuTc, Cu etc.Preferably, described copper catalyst is CuSO 45H 2o.Wherein, the consumption of described catalyzer is the 1-80mol% of raw material aromatic amine compounds (substrate 1) as shown in the formula (I).Preferably, described catalyst levels is the 10mol% of raw material aromatic amine compounds as shown in the formula (I).
In the present invention, described part is PPh 3, PtBu 3, tricyclohexyl phosphine, three furyl phosphines, dppm(1, two (diphenylphosphine) methane of 1-), dppe[1, two (diphenylphosphine) ethane of 2-], dppp[1, two (diphenylphosphine) propane of 3-], dppb[1, two (diphenyl phosphine) butane of 4-], dppf[1, two (diphenylphosphine) ferrocene of 1'-] or binap[2, two diphenyl phosphine-1 of 2'-, 1'-dinaphthalene], pyridine, 2, 2 '-dipyridyl, 4, 4'-dimethyl-2, 2'-dipyridyl, 4, 4 '-dipyridyl, 4, 4 '-di-t-butyl-2, 2 '-dipyridyl, 1, 10-phenanthroline, 2, 9-dimethyl-4, 7-biphenyl-1, 10-phenanthrolene, 4, 7-phenylbenzene-1, 10-phenanthroline etc.Preferably, described part is 2,2 '-dipyridyl.Wherein, described part consumption is the 1-80mol% of aromatic amine compounds (substrate 1) as shown in the formula (I).Preferably, the 10mol% that described part consumption is aromatic amine compounds as shown in the formula (I).
In the present invention, described reaction solvent is methyl alcohol, ethanol, Virahol, the trimethyl carbinol, water, DMSO, DMF, DMA, acetonitrile, acetone, tetrahydrofuran (THF), toluene, methylene dichloride, 1, any one of 2-ethylene dichloride, chloroform or arbitrary combination.Preferably, described solvent is methyl alcohol, water.
Building-up reactions of the present invention comprises the following steps: (1) adds sulfuration reagent, halogenated alkane, copper catalyst, solvent, stirring reaction under 0-100 ℃ of condition in reaction vessel; (2) reaction system step (1) being obtained is cooled to 0 ℃, adds aryl amine derivatives substrate, the alkyl nitriteester shown in formula (I), and stirring reaction under 0-100 ℃ of condition obtains the arylalkyl sulfide compound shown in formula (II).Preferably, step (1) is reacted at 80 ℃ of temperature.Preferably, step (2) is reacted at room temperature to 80 ℃ temperature.
In a specific examples, building-up reactions of the present invention is in reaction flask A, adds sulfuration reagent N a 2s 2o 3(X mmol), halogenide halogenated alkane (Y mmol), Catalysts Cu SO 45H 2o (Z mmol), part 2,2 '-dipyridyl (Ummol), solvent (V mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds arylamine chemicals (formula 1, W mmol), alkyl nitride (O mmol), reaction system, under the condition of room temperature to 80 ℃, stirs 4.5-24 hour.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (P mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 through column chromatography for separation.
The invention allows for the arylalkyl sulfide compound as shown in the formula (II) preparing according to the above-mentioned synthetic method of the present invention,
Figure BDA0000465014200000041
Wherein, Ar is phenyl ring, heterocycle, substituted benzene ring or substituted heterocycle; R is straight chained alkyl, branched paraffin or contains aromatic yl paraffin.
The invention allows for new arylalkyl sulfide compound, its structural formula as shown in the formula (II),
Figure BDA0000465014200000042
Wherein, Ar is 2-iodophenyl, 2-isopropyl phenyl, 2-chloro-4 nitrophenyl, 2-methyl-formiate-5-chloro-phenyl-, 3-chloro-phenyl-, 3-nitrophenyl, 3-nitro-4-methyl phenyl, 3-nitro-4-chloro-phenyl-, 3, 4, 5-trimethoxyphenyl, 3, 5-dioctyl phthalate methyl esters phenyl, 4-thiomethyl phenyl, 4-acetonitrile phenyl, 4-ethyl formate phenyl, 2-methyl-4-nitrophenyl, 4-carboxyl phenyl, 3-methane amide phenyl, 4-azobenzene phenyl, the trimethyl silicon based ethynyl phenyl of 4-, 4-ethynyl phenyl, pyridine, indoles, benzo lactone, fluorenes, 4-sulfanilamide (SN) phenyl, 4-replaces sulfanilamide (SN) phenyl, replace benzo lactan, amino acid derivative, sugar derivatives, R is 2,6-benzyl dichloride chlorine, 2,6-bis-trifluoromethyl benzyl chlorine, 4-fluorine benzyl chlorine, 4-bromobenzyl chlorine, 4-trifluoromethyl benzyl chlorine, 4-nitrobenzyl chlorine, substituted allyl, ether, n-pentyl.
Advantage of the present invention comprises: each raw material that synthetic method of the present invention is used is industrialization commodity, simple and easy to get, wide material sources, and performance is highly stable, does not need special preservation condition; The present invention's catalyzer used is copper catalyst cheap and easy to get, and ligand structure is simple, low price, and the two is convenience goods reagent, highly stable; The present invention uses colorless and odorless solid sulfur sodium thiosulfate as sulfuration reagent, has that cost is low, productive rate is high, technique is simple, pollute few characteristic, completely applicable to scale operation; The present invention uses alcohol, water as reaction solvent, environmental protection; Substrate universality of the present invention is wide, functional group's tolerance is strong; Synthetic method of the present invention (for example successfully realizes multiple drug molecules, embodiment 72-75), amino acid derivative (for example, embodiment 76), saccharide compound (for example, embodiment 77) later stage modify, for pharmaceutical chemistry and biological orthogonal chemical research provide reliably " later stage sulfuration " method, for pharmaceutical chemistry, biological orthogonal chemical research provide the efficient construction method of carbon-sulfur bond.Traditional method of synthesizing aryl alkyl thioether compound is generally to realize with mercaptan or thiophenol.But, because its taste is larger, easily oxidized, aftertreatment difficulty, seriously polluted, suitability for industrialized production is caused to very large restriction.The present invention is take the aromatic amine compounds easily prepared as reaction raw materials, with the Na of colorless and odorless 2s 2o 3salt is as sulfuration reagent, and under cheap α-benzoinoxime catalyst action, reaction obtains the arylalkyl sulfide compound replacing.Operation is simple, and reaction conditions gentleness is applicable to large-scale industrial production.
Embodiment
In conjunction with following specific embodiment, the present invention is described in further detail, and protection content of the present invention is not limited to following examples.Do not deviating under the spirit and scope of inventive concept, variation and advantage that those skilled in the art can expect are all included in the present invention, and take appending claims as protection domain.Implement process of the present invention, condition, reagent, experimental technique etc., except the content of mentioning specially below, be universal knowledege and the common practise of this area, the present invention is not particularly limited content.The given data of following examples comprise concrete operations and reaction conditions and product.Product purity is identified by nuclear-magnetism.
The building-up reactions of arylalkyl sulfide compound of the present invention, comprises the following steps: (1) adds sulfuration reagent, halogenated alkane, copper catalyst, solvent, stirring reaction under 0-100 ℃ of condition in reaction vessel; (2) reaction system step (1) being obtained is cooled to 0 ℃, adds aryl amine derivatives substrate, the alkyl nitriteester shown in formula (I), and stirring reaction under 0-100 ℃ of condition obtains the arylalkyl sulfide compound shown in formula (II).Drying, filtration, concentrated again, column chromatography for separation obtains object product.
Arylalkyl sulfide compound as shown in table 1, is by the inventive method and synthesizes the product obtaining, and there is not yet open source literature and discloses these compounds.
Table 1 new arylalkyl sulfide compound of the present invention
Figure BDA0000465014200000051
Figure BDA0000465014200000061
Figure BDA0000465014200000071
Embodiment 1
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000081
In reaction tubes, add CuCl (0.02mmol, 2.0mg), substrate 1 (0.2mmol, 24.6mg), BnCl (1.0mmol, 116 μ L), Na 2s 2o 35H 2o (1.0mmol, 248mg), nitrite tert-butyl (0.3mmol, 40 μ L), methanol/water (1mL/1mL), reaction system stirs 10 hours at ambient temperature, monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains transparent solid 2 (2.3mg, 5%), R through column chromatography for separation f=0.50 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.34 – 7.15 (m, 7H), 6.83 (d, J=7.8Hz, 2H), 4.02 (s, 2H), 3.81 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 159.12,138.05,134.02,128.83,128.30,126.92,125.95,114.34,55.23,41.15; IR (film) 2961,1494,1453,1266,1119,822,697cm -1.
Embodiment 2
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000082
In reaction tubes, add CuSO 45H 2o (0.02mmol, 5.1mg), substrate 1 (0.2mmol, 24.6mg), BnCl (1.0mmol, 116 μ L), Na 2s 2o 3(1.0mmol, 248mg), nitrite tert-butyl (0.3mmol, 40 μ L), methanol/water (1mL/1mL), reaction system stirs 10 hours at ambient temperature, monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains transparent solid 2 (4.1mg, 9%) through column chromatography for separation.
Embodiment 3
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000091
In reaction tubes, add Na 2s 2o 35H 2o (1.0mmol, 248mg), BnCl (1.0mmol, 116 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours under 80 ℃ of conditions; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, stirs 10 hours in room temperature to condition.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 (9.2mg, 20%) through column chromatography for separation.
Embodiment 4
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000092
In reaction tubes, add Na 2s 2o 35H 2o (1.0mmol, 248mg), BnCl (1.0mmol, 116 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 60 ℃ of conditions, stirs 10 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 (19.3mg, 42%) through column chromatography for separation.
Embodiment 5
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000093
In reaction tubes, add Na 2s 2o 35H 2o (1.0mmol, 248mg), BnCl (1.0mmol, 116 μ L), CuSO 45H 2-o (0.02mmol, 5.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 10 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 (20.7mg, 45%) through column chromatography for separation.
Embodiment 6
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000101
In reaction tubes, add Na 2s 2o 35H 2o (1.0mmol, 248mg), BnCl (1.0mmol, 116 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), L1 (0.02mmol, 11.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 10 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 (18.9mg, 41%) through column chromatography for separation.
Embodiment 7
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000102
In reaction tubes, add Na 2s 2o 35H 2o (1.0mmol, 248mg), BnCl (1.0mmol, 116 μ L), CuSO 45H 2-o (0.02mmol, 5.1mg), L2 (0.02mmol, 11.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 10 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 (11.0mg, 24%) through column chromatography for separation.
Embodiment 8
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000111
In reaction tubes, add Na 2s 2o 35H 2o (1.0mmol, 248mg), BnCl (1.0mmol, 116 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 10 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 (27.6mg, 60%) through column chromatography for separation.
Embodiment 9
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000112
In reaction tubes, add Na 2s 2o 35H 2o (1.0mmol, 248mg), BnCl (1.0mmol, 116 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), L4 (0.02mmol, 3.7mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 10 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 (21.6mg, 47%) through column chromatography for separation.
Embodiment 10
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.0mmol, 248mg), BnCl (1.0mmol, 116 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), L5 (0.02mmol, 3.6mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 10 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 (27.1mg, 59%) through column chromatography for separation.
Embodiment 11
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000121
In reaction tubes, add Na 2s 2o 35H 2o (1.0mmol, 248mg), BnCl (1.0mmol, 116 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), L6 (0.02mmol, 4.2mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 10 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 (18.9mg, 41%) through column chromatography for separation.
Embodiment 12
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000122
In reaction tubes, add Na 2s 2o 35H 2o (1.0mmol, 248mg), BnCl (1.0mmol, 116 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 (41.4mg, 90%) through column chromatography for separation.
Embodiment 13
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000131
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 (46.0mg, 99%) through column chromatography for separation.
Embodiment 14
Synthesizing of benzyl (4-fluorophenyl) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 3a (0.2mmol, 22.2mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains yellow solid 3 (41.4mg, 95%), R through column chromatography for separation f=0.65 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.44 – 7.03 (m, 7H), 6.86 (t, J=8.7Hz, 2H), 3.95 (s, 2H). 19f NMR (377MHz, CDCl 3) δ-114.89; 13c NMR (100MHz, CDCl 3) δ 163.32,160.87,137.52,133.42 (d, J=8.1Hz), 130.74 (d, J=3.3Hz), 128.63 (d, J=38.4Hz), 127.17,115.88 (d, J=21.8Hz), 40.45; IR (film) 1588,1488,1452,1225,1156,1090,824,697cm -1.
Embodiment 15
Synthesizing of benzyl (4-chloro-phenyl-) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 4a (0.2mmol, 25.4mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains colourless liquid 4 (37.9mg, 81%), R through column chromatography for separation f=0.65 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.24 – 7.16 (m, 5H), 7.14 (s, 4H), 4.01 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 137.13,134.68,132.51,131.47,128.94,128.78,128.53,127.29,39.36; IR (film) 2924,1476,1260,1095,1011,811,711,698cm -1.
Embodiment 16
Synthesizing of benzyl (4-bromophenyl) thioether:
Figure BDA0000465014200000142
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 5a (0.2mmol, 34.0mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains transparent solid 5 (36.0mg, 65%), R through column chromatography for separation f=0.65 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.39 (d, J=8.5Hz, 2H), 7.33 – 7.25 (m, 5H), 7.18 (d, J=8.5Hz, 2H), 4.11 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 137.03,135.42,131.84,131.48,128.76,128.53,127.30,120.31,39.09; IR (film) 2974,1453,1382,1088,1046,880cm -1.
Embodiment 17
Synthesizing of benzyl (phenyl) thioether:
Figure BDA0000465014200000151
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 6a (0.2mmol, 18.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains colourless liquid 6 (39.8mg, 99%), R through column chromatography for separation f=0.60 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.28 – 7.03 (m, 10H), 4.04 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 137.42,136.33,129.80,128.79 (d, J=1.0Hz); 128.45,127.14,126.31, IR (film) 1480,1408,1240,1090,1070,1030,920,740cm -1.
Embodiment 18
Synthesizing of benzyl (4-aminomethyl phenyl) thioether:
Figure BDA0000465014200000152
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 7a (0.2mmol, 21.4mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 7 (34.2mg, 80%), R through column chromatography for separation f=0.60 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.22 – 7.11 (m, 7H), 6.98 (d, J=8.0Hz, 2H), 3.99 (s, 2H), 2.23 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 137.80,136.56,132.48,130.72,129.59,128.81,128.41,127.04,39.80,21.01; IR (film) 3027,1492,1452,1237,1091,1017,802,765,697cm -1.
Embodiment 19
Synthesizing of benzyl (4-tert-butyl-phenyl) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 8a (0.2mmol, 29.8mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 24 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 8 (35.8mg, 70%), R through column chromatography for separation f=0.70 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.25 – 7.16 (m, 9H), 4.03 (s, 2H), 1.22 (s, 9H); 13c NMR (100MHz, CDCl 3) δ 149.66,137.72,132.88,129.87,128.82,128.44,127.08,125.87,39.44,34.46,31.25; IR (film) 2961,1494,1453,1267,1119,1014,822,698cm -1.
Embodiment 20
Synthesizing of benzyl (4-thiomethyl phenyl) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 9a (0.2mmol, 29.0mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 9 (32.3mg, 63%), R through column chromatography for separation f=0.55 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.23 – 7.11 (m, 7H), 7.05 (d, J=8.4Hz, 2H), 3.98 (s, 2H), 2.37 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 137.46,137.02,132.30,131.06,128.76,128.42,127.11,126.85,39.62,15.80; IR (film) 2919,1478,1453,1391,1263,1108,1009,851,739,710,696cm -1; HRMS (ESI) Calcd for C 14h 15s 2[M+H] +247.0610, Found247.0608.
Embodiment 21
Synthesizing of benzyl (4-acetonitrile-base phenyl) thioether:
Figure BDA0000465014200000171
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 10a (0.2mmol, 26.9mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains faint yellow solid 10 (29.6mg, 62%), R through column chromatography for separation f=0.15 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.24 – 7.11 (m, 9H), 4.04 (s, 2H), 3.61 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 137.04,136.63,130.17,128.74,128.53,128.34,127.80,127.29,117.60,38.78,23.18; IR (film) 3061,3028,2363,2252,1494,1453,1410,1264,1093,1016,793,738,711cm -1; HRMS (ESI) Calcd for C 15h 17n 2s[M+NH 4] +257.1107, Found257.1096.
Embodiment 22
Synthesizing of benzyl (4-itrile group phenyl) thioether:
Figure BDA0000465014200000172
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 11a (0.2mmol, 23.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains faint yellow solid 11 (31.0mg, 69%), R through column chromatography for separation f=0.20 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.42 (d, J=8.6Hz, 2H), 7.30 – 7.17 (m, 7H), 4.12 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 144.43,135.71,132.18,128.75,128.66,127.67,127.36,118.76,108.59,37.09; IR (film) 3083,2220,1589,1482,1453,1399,1086,1028,1014,818,781,718,700cm -1.
Embodiment 23
Synthesizing of benzyl (4-ethyl formate phenyl) thioether:
Figure BDA0000465014200000181
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 12a (0.2mmol, 33.5mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 12 (31.0mg, 57%), R through column chromatography for separation f=0.25 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.84 (d, J=8.4Hz, 2H), 7.24 (ddd, J=19.4,14.8,9.0Hz, 7H), 4.27 (q, J=7.1Hz, 2H), 4.13 (s, 2H), 1.30 (t, J=7.1Hz, 3H); 13c NMR (100MHz, CDCl 3) δ 166.25,143.47,136.30,129.83,128.72,128.63,127.44,127.39,126.91,60.88,37.27,14.30; IR (film) 2098,1711,1593,1271,1179,1106,1017,758,693cm -1.
Embodiment 24
Synthesizing of benzyl (2-fluorophenyl) thioether:
Figure BDA0000465014200000182
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 13a (0.2mmol, 22.2mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 13 (38.4mg, 88%), R through column chromatography for separation f=0.65 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.22 – 7.09 (m, 7H), 6.96 (ddt, J=13.8,7.5,3.8Hz, 2H), 4.02 (s, 2H). 19f NMR (377MHz, CDCl 3) δ-109.09; 13c NMR (100MHz, CDCl 3) δ 161.64 (d, J=245.4Hz), 137.15; 132.97 (d, J=1.8Hz), 128.81; 128.75,128.43,127.22; 124.31 (d, J=3.7Hz), 122.68 (d; J=17.8 Hz), 115.57 (d, J=22.5Hz); 38.35 (d, J=2.7Hz); IR (film) 3064,3030,1472,1449,1260,1221,1071,1029,821,753,699cm -1.
Embodiment 25
Synthesizing of benzyl (2-chloro-phenyl-) thioether:
Figure BDA0000465014200000191
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2-O (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 14a (0.2mmol, 22.2mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains colourless liquid 14 (39.8mg, 85%), R through column chromatography for separation f=0.65 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.30 – 7.14 (m, 7H), 7.05 (dtd, J=18.8,7.4,1.6Hz, 2H), 4.07 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 136.27,135.70,133.62,129.59,129.20,128.88,128.55,127.36,127.04,126.82,37.43; IR (film) 3060,3029,1494,1451,1114,1034,743,696cm -1.
Embodiment 26
Synthesizing of benzyl (2-bromophenyl) thioether:
Figure BDA0000465014200000192
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 15a (0.2mmol, 22.2mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 15 (36.4mg, 67%), R through column chromatography for separation f=0.60 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.48 – 7.44 (m, 1H), 7.28 (d, J=7.1Hz, 2H), 7.25 – 7.10 (m, 5H), 6.97 – 6.91 (m, 1H), 4.06 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 137.82,136.04,132.86,128.91,128.68,128.56,127.67,127.39,126.83,123.53,37.82; IR (film) 2922,1493,1448,1258,1106,1020,741,716,696cm -1.
Embodiment 27
Synthesizing of benzyl (2-iodophenyl) thioether:
Figure BDA0000465014200000201
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 16a (0.2mmol, 43.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system at ambient temperature, stirs 24 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains orange solids 16 (41.8mg, 64%), R through column chromatography for separation f=0.65 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.56 (t, J=1.7Hz, 1H), 7.42 (dd, J=7.8,1.0Hz, 1H), 7.25 – 7.12 (m, 6H), 6.88 (t, J=7.9Hz, 1H), 4.02 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 138.82,137.78,136.74,135.15,130.21,128.82,128.59,128.55,127.37,94.41,38.78; IR (film) 3059,3028,2922,1566,1550,1493,1454,1391,1237,1059,768,737,697,677cm -1; HRMS (EI) Calcd for C 13h 11sCI325.9626, Found325.9629.
Embodiment 28
Synthesizing of benzyl (3-chloro-phenyl-) thioether:
Figure BDA0000465014200000202
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 17a (0.2mmol, 25.4mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 17 (44.5mg, 95%), R through column chromatography for separation f=0.70 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.21 (t, J=9.7Hz, 6H), 7.08 (d, J=1.2Hz, 3H), 4.05 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 138.58,136.77,134.55,129.79,129.02,128.81,128.58,127.41,127.39,126.32,38.70; IR (film) 3061,3029,1577,1461,1085,1071,776,697,678cm -1; HRMS (EI) Calcd for C 13h 11sCl234.0270, Found234.0272.
Embodiment 29
Synthesizing of benzyl (3-nitrophenyl) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 18a (0.2mmol, 27.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains yellow solid 18 (30.9mg, 63%), R through column chromatography for separation f=0.40 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 8.05 (t, J=1.9Hz, 1H), 7.91 (dd, J=8.2,1.3Hz, 1H); 7.47 (ddd, J=7.8,1.6,0.9Hz, 1H), 7.32 (t; J=8.0Hz, 1H), 7.27 – 7.16 (m, 5H), 4.13 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 148.45,139.37,136.04,134.62,129.41,128.80,128.71,127.64,123.20,120.80,38.30; IR (film) 3085,2924,1522,1453,1126,1068,877,780,747,729,669cm -1; HRMS (EI) Calcd for C 13h 11nO 2s245.0511, Found245.0505.
Embodiment 30
Synthesizing of benzyl (2,6-3,5-dimethylphenyl) thioether:
Figure BDA0000465014200000212
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 19a (0.2mmol, 24.2mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains colourless liquid 19 (23.7mg, 52%), R through column chromatography for separation f=0.75 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.16 – 7.10 (m, 3H), 7.07 – 6.96 (m, 5H), 3.71 (s, 2H), 2.31 (s, 6H); 13c NMR (100MHz, CDCl 3) δ 143.57,138.39,132.75,128.76,128.41,128.24,127.96,126.87,39.78,21.78; IR (film) 3058,3028,2922,2852,1493,1457,1375,1055,1029,769,697cm -1.
Embodiment 31
Synthesizing of benzyl (2-isopropyl phenyl) thioether:
Figure BDA0000465014200000221
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 20a (0.2mmol, 27.0mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains colourless liquid 20 (24.2mg, 50%), R through column chromatography for separation f=0.80 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.27 – 7.23 (m, 1H), 7.22 – 7.09 (m, 7H), 7.03 (td, J=7.5; 1.6Hz, 1H), 3.99 (s, 2H), 3.37 (dt, J=13.7; 6.9Hz, 1H), 1.08 (d, J=6.9Hz, 6H); 13c NMR (100MHz, CDCl 3) δ 148.86,137.38,134.41,130.25,128.86,128.43,127.12,126.80,126.17,125.42,39.53,30.16,23.32; IR (film) 2960,2926,1470,1452,1438,1052,1030,752,696cm -1; HRMS (EI) Calcd for C 16h 18s242.1129, Found242.1125.
Embodiment 32
Synthesizing of benzyl (2-methyl-4-nitrophenyl) thioether:
Figure BDA0000465014200000231
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 21a (0.2mmol, 31.7mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains yellow solid 21 (46.5mg, 90%), R through column chromatography for separation f=0.45 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.90 (d, J=6.2Hz, 2H), 7.35 – 7.15 (m, 6H), 4.16 (s, 2H), 2.29 (s, 3H), 13c NMR (100MHz, CDCl 3) δ 146.73,144.62,136.25,135.14,128.81,128.78,127.80,124.35,124.26,121.47,36.60,20.00; IR (film) 2925,1574,1496,1335,1059,911,800,741,714,693cm -1; HRMS (ESI) Calcd for C 14h 14nO 2s[M+H] +260.0740, Found260.0732.
Embodiment 33
Synthesizing of benzyl (3-nitro-4-methyl phenyl) thioether:
Figure BDA0000465014200000232
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 22a (0.2mmol, 30.4mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains yellow solid 22 (34.2mg, 66%), R through column chromatography for separation f=0.50 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.91 (d, J=1.8Hz, 1H), 7.39 (dd, J=8.0,1.8Hz; 1H), 7.35 – 7.25 (m, 5H), 7.22 (d, J=8.0Hz; 1H), 4.17 (s, 2H), 2.56 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 149.13,136.34,135.72,133.89,132.98,131.36,128.79,128.62,127.51,125.05,38.66,20.08; IR (film) 1522,1452,1348,1120,799,710cm -1; HRMS (ESI) Calcd for C 14h 14nO 3s[M+H] +276.0689, Found276.0680.
Embodiment 34
Synthesizing of benzyl (2-chloro-4 nitrophenyl) thioether:
Figure BDA0000465014200000241
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 23a (0.2mmol, 34.9mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains yellow solid 23 (39.8mg, 71%), R through column chromatography for separation f=0.50 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 8.41 (d, J=2.4Hz, 1H), 8.15 (dd, J=8.9,2.4Hz, 1H), 7.49 (d, J=8.9Hz, 1H), 7.36 (ddd, J=26.6,18.0,10.1Hz, 5H), 4.73 (s, 2H), 13c NMR (100MHz, CDCl 3) δ 150.66,147.43,134.50,132.71,129.30,128.79,127.70,126.23,122.68,118.55,39.76; IR (film) 3092,1513,1411,1335,1115,1046,899,770,743,696cm -1; HRMS (ESI) Calcd for C 13h 11n 3o 2s[M+H] +305.0255, Found305.0255.
Embodiment 35
Synthesizing of benzyl (3-nitro-4-chloro-phenyl-) thioether:
Figure BDA0000465014200000242
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 24a (0.2mmol, 35.0mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains yellow solid 24 (45.3mg, 81%), R through column chromatography for separation f=0.45 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.65 (d, J=2.0Hz, 1H), 7.32 – 7.17 (m, 7H), 4.08 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 149.13,136.34,135.72,133.89,132.98,131.36,128.79,128.62,127.51,125.05,38.66,20.08; IR (film) 1530,1466,1454,1349,1105,1044,820,767,697cm -1.HRMS (EI) Calcd for C 13h 10nO 2sCl279.0120, Found279.0118.
Embodiment 36
Synthesizing of benzyl (3,4,5-trimethoxyphenyl) thioether:
Figure BDA0000465014200000251
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 25a (0.2mmol, 36.8mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 25 (30.8mg, 52%), R through column chromatography for separation f=0.60 (PE:EA=5:1); 1h NMR (400MHz, CDCl 3) δ 7.19 (ddd, J=5.9,4.6,1.3Hz, 5H), 6.43 (s, 2H), 3.98 (s, 2H), 3.74 (s, 3H), 3.68 (s, 6H); 13c NMR (100MHz, CDCl 3) δ 153.10,137.83,137.37,130.34,128.91,128.44,127.12,108.61,60.85,56.06,40.32; IR (film) 2935,1577,1496,1403,1307,1230,1123,1005,699cm -1; HRMS (ESI) Calcd for C 16h 19o 3s[M+H] +291.1049, Found291.1049.
Embodiment 37
Synthesizing of benzyl (3,5-dioctyl phthalate methyl esters phenyl) thioether:
Figure BDA0000465014200000252
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 26a (0.2mmol, 42.7mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 24 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 26 (37.8mg, 62%), R through column chromatography for separation f=0.60 (PE:EA=5:1); 1h NMR (400MHz, CDCl 3) δ 8.36 (t, J=1.5Hz, 1H), 8.04 (d, J=1.5Hz, 2H), 7.21 (qd, J=8.7,6.7Hz, 5H), 4.12 (s, 2H), 3.85 (s, 6H), 13c NMR (100MHz, CDCl 3) δ 165.72,138.23,136.33,133.82,131.06,128.85,128.59,128.08,127.46,52.41,38.37; IR (film) 2952,1727,1438,1316,1245,753cm -1; HRMS (ESI) Calcd for C 17h 17o 4s[M+H] +317.0842, Found317.0843.
Embodiment 38
Synthesizing of benzyl (2-methyl-formiate-5-chloro-phenyl-) thioether:
Figure BDA0000465014200000261
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 27a (0.2mmol, 37.0mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 27 (32.7mg, 62%), R through column chromatography for separation f=0.45 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.84 (d, J=8.4Hz, 1H), 7.37 – 7.32 (m, 2H), 7.28 – 7.22 (m, 3H), 7.22 – 7.17 (m, 1H), 7.05 (dd, J=8.4,2.0Hz, 1H), 4.07 (s, 2H), 3.81 (s, 3H) 13c NMR (100MHz, CDCl 3) δ 166.06,144.50,138.97,135.30,132.49,129.16,128.70,127.58,125.37 (d, J=2.3Hz), 124.09,52.19,37.38; IR (film) 3028,1676,1602,1474,1440,1327,1287,1241,1207,793,766,697cm -1; HRMS (EI) Calcd for C 11h 17o 2sCl292.0325, Found292.0324.
Embodiment 39
Synthesizing of benzyl (2-ethyl formate phenyl) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 28a (0.2mmol, 37.0mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 28 (32.7mg, 62%), R through column chromatography for separation f=0.45 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.84 (d, J=8.4Hz, 1H), 7.37 – 7.32 (m, 2H), 7.28 – 7.22 (m, 3H), 7.22 – 7.17 (m, 1H), 7.05 (dd, J=8.4,2.0Hz, 1H), 4.07 (s, 2H), 3.81 (s, 3H) 13c NMR (100MHz, CDCl 3) δ 166.06,144.50,138.97,135.30,132.49,129.16,128.70,127.58,125.37 (d, J=2.3Hz), 124.09,52.19,37.38; IR (film) 3028,1676,1602,1474,1440,1327,1287,1241,1207,793,766,697cm -1; HRMS (EI) Calcd for C 11h 17o 2sCl292.0325, Found292.0324.
Embodiment 40
Synthesizing of benzyl (4-carboxyl phenyl) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 29a (0.2mmol, 27.4mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 29 (39.0mg, 80%), R through column chromatography for separation f=0.25 (DCM:MeOH=25:1); 1h NMR (400MHz, DMSO) δ 7.82 (d, J=8.5Hz, 2H), 7.44 – 7.38 (m, 4H), 7.31 (t, J=7.4Hz, 2H), 7.25 (d, J=7.2Hz, 1H), 4.34 (s, 2H), 13c NMR (100MHz, DMSO) δ 166.94,143.03,136.79,129.71,128.86,128.49,127.46,127.24,126.46,35.39; IR (film) 3444,2926,1688,1587,1416,1320,1282,1026,840,763,716,691cm -1; HRMS (ESI) Calcd for C 14h 13o 2s[M+H] +245.0631, Found245.0629.
Embodiment 41
Synthesizing of benzyl (3-acetylphenyl) thioether:
Figure BDA0000465014200000281
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 30a (0.2mmol, 27.7mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 30 (40.3mg, 83%), R through column chromatography for separation f=0.25 (DCM:MeOH=25:1); 1h NMR (400MHz, CDCl 3) δ 7.60 (s, 1H), 7.53 (d, J=7.7Hz, 1H), 7.37 (d, J=7.8Hz, 1H), 7.27 – 7.15 (m, 6H), 6.02 (s, 2H), 4.06 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 168.94,137.17,136.94,133.90,133.07,129.02,128.89,128.53,128.50,127.32,125.21,38.76; IR (film) 3375,3169,1654,1620,1569,1428,1382,1124,786,719,694,672cm -1; HRMS (ESI) Calcd for C 14h 14nOS[M+H] +244.0791, Found244.0788.
Embodiment 42
Synthesizing of benzyl (4-hydroxy phenyl) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 31a (0.2mmol, 22.0mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system at ambient temperature, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 31 (22.9mg, 52%), R through column chromatography for separation f=0.45 (PE:EA=5:1); 1h NMR (400MHz, CDCl 3) δ 7.20 – 7.05 (m, 7H), 6.66 – 6.58 (m, 2H), 5.34 (s, 1H), 3.89 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 155.27,138.04,134.35,128.87,128.33,126.96,126.10,115.89,41.23; IR (film) 3425,1600,1588,1494,1430,1365,1256,817,711,697cm -1.
Embodiment 43
Synthesizing of benzyl (2-hydroxy phenyl) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 32a (0.2mmol, 21.8mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains brown solid 32 (18.6mg, 43%), R through column chromatography for separation f=0.70 (PE:EA=5:1); 1h NMR (400MHz, CDCl 3) δ 7.21 – 7.13 (m, 5H), 7.00 (dd, J=6.6,2.8Hz, 2H), 6.88 – 6.82 (m, 1H), 6.72 (td, J=7.5,1.2Hz, 1H), 6.46 (s, 1H), 3.76 (s, 2H) 13c NMR (100MHz, CDCl 3) δ 157.06,137.52,136.39,131.38,128.74,128.50,127.38,120.59,118.10,114.68,41.31; IR (film) 2925,1588,1493,1454,1223,1154,1087,837,767,693cm -1.
Embodiment 44
Synthesizing of benzyl (2-hydroxymethyl phenyl) thioether:
Figure BDA0000465014200000292
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 33a (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 33 (20.7mg, 45%), R through column chromatography for separation f=0.45 (PE:EA=5:1); 1h NMR (400MHz, CDCl 3) δ 7.30 (ddd, J=9.1,5.6,3.9Hz, 2H), 7.22 – 7.14 (m, 5H), 7.14 – 7.09 (m, 2H), 4.54 (s, 2H), 3.99 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 141.68,137.32,134.03,131.77,128.74,128.51,128.42,128.29,127.33,127.30,63.58,39.83; IR (film) 3355,2923,1494,1451,1193,1068,1031,1008,748,697cm -1.
Embodiment 45
Synthesizing of benzyl (4-nitrophenyl) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 34a (0.2mmol, 27.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains yellow solid 34 (47.5mg, 97%), R through column chromatography for separation f=0.40 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 8.02 (d, J=8.9Hz, 2H), 7.26 (dd, J=16.5,9.2Hz, 7H), 4.18 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 147.23,145.10,135.34,128.80,128.66,127.76,126.48,123.88,36.90; IR (film) 1576,1510,1338,1091,853,741,721cm -1.
Embodiment 46
Synthesizing of benzyl (2-benzophenone phenyl) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 35a (0.2mmol, 39.4mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains yellow solid 35 (44.5mg, 73%) as a white solid, R through column chromatography for separation f=0.70 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.69 – 7.63 (m, 2H), 7.48 (d, J=7.4Hz, 1H), 7.38 – 7.31 (m, 3H), 7.30 – 7.24 (m, 2H), 7.19 (dd, J=7.2,1.0Hz, 1H), 7.15 – 7.09 (m, 5H), 3.96 (s, 2H) 13c NMR (100MHz, CDCl 3) δ 196.75,140.66,137.32,136.82,135.42,133.08,131.15,130.40,130.05,128.94,128.37,127.14,125.94,39.62; IR (film) 3060,3027,1658,1598,1450,1316,1276,918,764,696cm -1.
Embodiment 47
Synthesizing of compound 36:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 36a (0.2mmol, 39.4mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system at ambient temperature, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains brown solid 36 (33.3mg, 51%), R through column chromatography for separation f=0.40 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.60 (d, J=8.1Hz, 2H), 7.21 (dd, J=14.1,7.7Hz, 7H), 4.08 (s, 2H), 1.25 (s, 12H), 13c NMR (100MHz, CDCl 3) δ 140.68,136.95,135.06,128.75,128.50,127.34,127.21,83.74,37.72,24.82; IR (film) 2978,1600,1393,1359,1321,1248,1143,1100,859,698cm -1.
Embodiment 48
Synthesizing of compound 37:
Figure BDA0000465014200000312
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 37a (0.2mmol, 40.0mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains red solid 37 (36.0mg, 60%), R through column chromatography for separation f=0.80 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.85 – 7.80 (m, 2H), 7.76 (d, J=8.5Hz, 2H), 7.41 (dd, J=13.0,7.3Hz, 3H), 7.31 (dd, J=10.6,8.1Hz, 4H), 7.24 (t, J=7.3Hz, 2H), 7.21 – 7.15 (m, 2H), 4.15 (s, 2H) 13c NMR (100MHz, CDCl 3) δ 152.59,150.50,140.94,136.61,130.89,129.07,128.78,128.62,128.44,127.41,123.30,122.76,37.96; IR (film) 3061,2924,1582,1482,1453,1220,1153,1070,926,775,690cm -1.HRMS (EI) Calcd for C 19h 16n 2s304.1034, Found304.1039.
Embodiment 49
Synthesizing of compound 38:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 38a (0.2mmol, 38.8mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains yellow solid 38 (30.4mg, 60%), R through column chromatography for separation f=0.25 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.54 (d, J=16.0Hz, 1H), 7.32 (d, J=7.9Hz, 2H), 7.28 – 7.15 (m, 7H), 6.30 (d, J=16.0Hz, 1H), 4.18 (q, J=7.1Hz, 2H), 4.09 (s, 2H), 1.25 (t, J=7.1Hz, 3H) 13c NMR (100MHz, CDCl 3) δ 166.97,143.79,139.85,136.71,131.99,128.73,128.58,128.54,128.35,127.36,117.71,60.45,37.99,14.29; IR (film) 3028,1707,1633,1591,1493,1309,1267,1170,1088,1033,981,814,697cm -1; HRMS (ESI) Calcd for C 18h 19o 2s[M+H] +299.1100, Found299.1101.
Embodiment 50
Synthesizing of compound 39:
Figure BDA0000465014200000322
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 39a (0.2mmol, 39.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system at ambient temperature, stirs 24 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 39 (40.3mg, 60%), R through column chromatography for separation f=0.80 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.36 (d, J=8.3Hz, 2H), 7.31 (d, J=4.2Hz, 4H), 7.28 (s, 1H), 7.22 (d, J=8.3Hz, 2H), 4.15 (s, 2H), 0.26 (s, 9H), 13c NMR (100MHz, CDCl 3) δ 137.44,136.82,132.21,128.75,128.56,128.54,127.30,120.54,104.63,94.65,38.27 ,-0.07; IR (film) 3028,2154,1492,1452,1249,1069,861,842,761,695cm -1; HRMS (ESI) Calcd for C 18h 21sSi[M+H] +299.1128, Found299.1117.
Embodiment 51
Synthesizing of compound 40:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 40a (0.2mmol, 23.4mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system at ambient temperature, stirs 24 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 40 (19.3mg, 43%), R through column chromatography for separation f=0.80 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.29 (d, J=8.3Hz, 2H), 7.22 (dd, J=11.8,9.0Hz, 5H), 7.15 (d, J=8.4Hz, 2H), 4.07 (s, 2H), 3.01 (s, 1H); 13c NMR (100MHz, CDCl 3) δ 138.01,136.74,132.38,128.75,128.57,128.45,127.34,119.44,83.25,77.58,38.17; IR (film) 3278,2923,2104,1590,1489,1088,1014,815,779,719cm -1; HRMS (EI) Calcd for C 15h 12s224.0660, Found224.0663.
Embodiment 52
Synthesizing of compound 41:
Figure BDA0000465014200000341
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 41a (0.2mmol, 18.8mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 41 (20.5mg, 51%), R through column chromatography for separation f=0.70 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 8.45 (s, 1H), 8.35 (d, J=4.2Hz, 1H), 7.52 – 7.45 (m, 1H), 7.25 – 7.14 (m, 5H), 7.09 (dd, J=7.9,4.8Hz, 1H), 4.03 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 151.10,147.53,138.17,136.78,133.07,128.80,128.58,127.44,123.48,39.22; IR (film) 2925,1703,1574,1482,1403,1276,1220,1107,1065,1012,801,713cm -1; HRMS (ESI) Calcd for C 12h 12nS[M+H] +202.0685, Found202.0683.
Embodiment 53
Synthesizing of compound 42:
Figure BDA0000465014200000342
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 42a (0.2mmol, 57.2mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 42 (34.3mg, 43%), R through column chromatography for separation f=0.30 (PE:EA=5:1); 1h NMR (400MHz, CDCl 3) δ 7.78 (d, J=8.0Hz, 1H); 7.66 (d, J=8.4Hz, 2H); 7.47 (d, J=3.7Hz, 1H); 7.16 – 7.04 (m, 9H), 6.65 (d; J=3.7Hz, 1H), 4.01 (s; 2H), 2.25 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 145.03,137.21,135.22 – 135.10 (m), 134.46,131.56,129.85,128.73,128.60,128.37,127.13,126.77,126.26,125.02,124.83,112.14,107.83,38.88,21.54; IR (film) 1596,1465,1411,1371,1194,1168,1131,1004,754,701,677cm -1; HRMS (ESI) Calcd for C 22h 23n 2o 2s 2[M+NH 4] +411.1195, Found411.1196.
Embodiment 54
Synthesizing of compound 43:
Figure BDA0000465014200000351
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 43a (0.2mmol, 30.0mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 24 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 43 (37.2mg, 70%), R through column chromatography for separation f=0.40 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.75 (s, 1H), 7.46 (d, J=1.6Hz, 1H), 7.30 – 7.14 (m, 6H), 5.19 (s, 2H), 4.10 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 170.36,144.24,138.67,136.32,135.12,128.77,128.61,127.49,126.61,125.56,122.29,69.47,38.65; IR (film) 2960,2924,1743,1452,1301,1261,1193,1081,1045,795,723,695cm -1; HRMS (ESI) Calcd for C 15h 13o 2s[M+H] +257.0631, Found257.0631.
Embodiment 55
Synthesizing of compound 44:
Figure BDA0000465014200000352
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 44a (0.2mmol, 30.0mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 24 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 44 (39.2mg, 68%), R through column chromatography for separation f=0.80 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.65 (d, J=7.5Hz, 1H), 7.57 (d, J=7.9Hz, 1H); 7.43 (d, J=7.4Hz, 1H), 7.40 (s, 1H), 7.30 – 7.14 (m; 8H), 4.06 (s, 2H), 3.75 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 143.89,143.07,141.14,140.50,137.65,134.22,129.22,128.86,128.43,127.26,127.11,126.81,126.78,125.02,120.07,119.83,39.86,36.72; IR (film) 3060,3028,2923,1604,1493,1449,1411,1070,1024,814,762,731,711,696cm -1; HRMS (ESI) CalcdforC 20h 17s[M+H] +289.1045, Found289.1033.
Embodiment 56
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnBr (1.4mmol, 239.4mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 2 (46.0mg, 99%) through column chromatography for separation.
Embodiment 57
Synthesizing of compound 46:
Figure BDA0000465014200000362
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 46b (1.4mmol, 201.6mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains target product 46 (33.2mg, 67%), R through column chromatography for separation f=0.50 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.17 – 7.12 (m, 2H), 7.04 (dd, J=8.6,5.4Hz, 2H), 6.85 (t, J=8.7Hz, 2H), 6.74 – 6.69 (m, 2H), 3.86 (s, 2H), 3.70 (s, 3H); 19f NMR (377MHz, CDCl 3) δ-115.69 (d, J=0.9Hz); 13c NMR (100MHz, CDCl 3) δ 161.86 (d, J=245.3Hz), 159.35,134.34,133.93 (d, J=3.2Hz), 130.37 (d, J=8.1Hz), 125.58,115.13 (d, J=21.4Hz), 114.46,55.27,40.49; IR (film) 3012,2956,2922,2837,1597,1511,1492,1437,1286,1238,1179,1155,1029,844,756,695cm -1; HRMS (EI) Calcd for C 14h 13oFS248.0671, Found248.0674.
Embodiment 58
Synthesizing of compound 47:
Figure BDA0000465014200000371
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 47b (1.4mmol, 284.2mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 47 (32.5mg, 53%), R through column chromatography for separation f=0.50 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.28 (d, J=8.4Hz, 2H), 7.15 (d, J=8.7Hz, 2H), 6.95 (d, J=8.3Hz, 2H), 6.71 (d, J=8.7Hz, 2H), 3.82 (s, 2H), 3.70 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 159.40,137.31,134.39,131.39,130.51,125.36,120.80,114.50,55.28,40.65; IR (film) 3017,2957,2925,2837,1592,1490,1457,1286,1250,1177,1071,1028,1011,810,750cm -1; HRMS (EI) Calcd for C 14h 13oBrS307.9870, Found307,9869.
Embodiment 59
Synthesizing of compound 48:
Figure BDA0000465014200000372
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 48b (1.4mmol, 284.2mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 48 (40.5mg, 68%), R through column chromatography for separation f=0.50 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.38 (d, J=7.0Hz, 1H), 7.27 (d, J=7.1Hz, 3H), 7.16 – 7.11 (m, 2H), 6.74 – 6.68 (m, 2H), 3.90 (s, 2H), 3.70 (s, 3H); 19f NMR (377MHz, CDCl 3) δ-62.68; 13c NMR (101MHz, CDCl 3) δ 159.64,139.27,134.79,132.17,130.57 (d, J=32.1Hz); 128.75,125.74 – 125.47 (m), 125.37,124.89,123.72 (q; J=3.8Hz), 122.66,114.55,55.28,40.99; IR (film) 1592,1493,1449,1330,1247,1166,1224,1073,826,802,701cm -1; HRMS (ESI) Calcd for C 15h 14f 3oS[M+H] +299.0712, Found299.0716.
Embodiment 60
Synthesizing of compound 49:
Figure BDA0000465014200000381
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 49b (1.4mmol, 239.4mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains brown solid 49 (22.0mg, 68%), R through column chromatography for separation f=0.30 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 8.00 (d, J=8.7Hz, 2H), 7.18 (d, J=8.7Hz, 2H), 7.12 (d, J=8.8Hz, 2H), 6.70 (d, J=8.8Hz, 2H), 3.91 (s, 2H), 3.69 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 159.63,146.72,146.09,134.87,129.53,124.09,123.47,114.52,55.21,40.72; IR (film) 2958,2926,2852,1739,1593,1517,1492,1344,1244,1105,1028,857,824,800,724cm -1; HRMS (EI) Calcd for C 14h 13nO 3s275.0616, Found275.0615.
Embodiment 61
Synthesizing of compound 50:
Figure BDA0000465014200000391
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 50b (1.4mmol, 254.8mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 50 (29.7mg, 52%), R through column chromatography for separation f=0.60 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.21 (dd, J=7.6,4.6Hz, 4H), 7.08 (d, J=7.8Hz, 2H), 6.73 (d, J=8.2Hz, 2H), 3.91 (s, 2H), 3.71 (s, 3H), 1.22 (s, 9H); 13c NMR (100MHz, CDCl 3) δ 159.06,149.96,134.90,133.61,128.50,126.67,125.31,114.42,55.30,40.72,34.46,31.33; IR (film) 2960,1592,1493,1462,1284,1244,1176,1033,825cm -1; HRMS (ESI) Calcd for C 18h 23oS[M+H] +287.1464, Found287.1462.
Embodiment 62
Synthesizing of compound 51:
Figure BDA0000465014200000392
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 51b (1.4mmol, 201.6mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains colourless liquid 51 (27.3mg, 55%), R through column chromatography for separation f=0.55 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.19 – 7.08 (m, 3H), 6.88 – 6.79 (m, 3H), 6.74 – 6.69 (m, 2H), 3.87 (s, 2H), 3.70 (s, 3H); 19f NMR (377MHz, CDCl 3) δ-113.39; 13c NMR (100MHz, CDCl 3) δ 162.71 (d, J=245.8 Hz), 159.41; 140.79 (d, J=7.4Hz), 134.30; 129.71 (d, J=8.3Hz), 125.45; 124.49 (d, J=2.8Hz), 115.70 (d; J=21.7Hz), 114.50,113.87 (d; J=21.1Hz), 55.28,40.83; IR (film) 2929,1616,1591,1493,1445,1286,1247,1177,1032,945,827,786,742cm -1; HRMS (ESI) Calcd for C 14h 14fOS[M+H] +249.0744, Found249.0742.
Embodiment 63
Synthesizing of compound 52:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 52b (1.4mmol, 271.4mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains colourless liquid 52 (41.6mg, 70%), R through column chromatography for separation f=0.50 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.28 (d, J=8.5Hz, 2H), 7.18 (d, J=7.9Hz, 2H), 7.02 (t, J=8.0Hz, 1H), 6.72 (d, J=8.5Hz, 2H), 4.21 (s, 2H), 3.72 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 159.88,135.88,135.73,134.50,128.48,128.22,125.09,114.36,55.31,36.97; IR (film) 2938,2835,1590,1492,1435,1284,1244,1173,1031,882,826,778,761; HRMS (EI) Calcd for C 14h 12oSCl 2297.9986, Found297.9990.
Embodiment 64
Synthesizing of compound 53:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 53b (1.4mmol, 366.8mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains colourless liquid 53 (52.0mg, 70%), R through column chromatography for separation f=0.50 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.64 (s, 1H), 7.41 (s, 2H), 7.14 – 7.08 (m, 2H), 6.75 – 6.69 (m, 2H), 3.92 (s, 2H), 3.70 (s, 3H); 19f NMR (377MHz, CDCl 3) δ-62.91; 13c NMR (100MHz, CDCl 3) δ 160.03,140.91,135.49,131.39 (q, J=33.3Hz), 128.98,124.52,123.60,121.81,121.12 – 120.18 (m), 114.70,55.31,40.82; IR (film) 1592,1493,1375,1278,1248,1171,1131,1031,899,827,705,682; HRMS (ESI) Calcd for C 16h 16f 6oS[M+H] +367.0586, Found367.0588.
Embodiment 65
Synthesizing of compound 54:
Figure BDA0000465014200000411
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 54b (1.4mmol, 166.6mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains brown solid 54 (29.0mg, 81%), R through column chromatography for separation f=0.45 (PE:EA=5:1); 1h NMR (400MHz, CDCl 3) δ 7.48 (d, J=8.7Hz, 2H), 6.84 (d, J=8.7Hz, 2H), 3.75 (s, 3H), 3.38 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 160.93,135.99,122.22,116.66,115.17,55.38 (d, J=1.5Hz), 22.86; IR (film) 2966,2931,2838,2244,1591,1493,1287,1247,1175,1027,826,800.
Embodiment 66
Synthesizing of compound 55:
Figure BDA0000465014200000412
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 55b (1.4mmol, 156.8mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains brown liquid 55 (16.2mg, 45%), R through column chromatography for separation f=0.40 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.27 (d, J=8.9Hz, 2H), 6.77 (d, J=8.8Hz, 2H), 5.77 (ddd; J=16.9,7.1,3.0Hz, 1H), 4.97 – 4.88 (m, 2H); 3.72 (s, 3H), 3.36 (dd, J=7.0,0.9Hz, 2H); 13c NMR (100MHz, CDCl 3) δ 159.03,133.95 (d, J=8.3Hz), 125.72,117.26,114.37,55.28,39.33; IR (film) 2960,2925,2854,1491,1258,1087,1013,793.
Embodiment 67
Synthesizing of compound 56:
Figure BDA0000465014200000421
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 56b (1.4mmol, 274.4mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 56 (26.1mg, 51%), R through column chromatography for separation f=0.45 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.29 (d, J=8.3Hz, 2H), 7.24 – 7.17 (m; 4H), 7.14 (dd, J=4.9; 2.8Hz, 1H), 6.75 (d; J=8.4Hz, 2H), 6.25 – 6.08 (m; 2H), 3.71 (s, 3H); 3.51 (d, J=6.3Hz, 2H); 13c NMR (100MHz, CDCl 3) δ 159.24,136.90,134.40,132.45,128.48,127.44,126.28,125.70,125.57,114.45,55.30,39.24; IR (film) 3031,3000,2954,2910,2984,1595,1494,1460,1435,1248,1030,968,818,759,690.
Embodiment 68
Synthesizing of compound 57:
Figure BDA0000465014200000431
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 57b (1.4mmol, 268.8mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains colourless liquid 57 (30.2mg, 60%), R through column chromatography for separation f=0.45 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.30 – 7.24 (m, 2H), 6.83 (d, J=15.4Hz; 1H), 6.79 – 6.73 (m, 2H), 5.58 (d; J=15.4Hz, 1H), 4.09 (q, J=7.1Hz; 2H), 3.73 (s, 3H), 3.42 (dd; J=7.4,1.2Hz, 2H); 1.20 (t, J=7.1Hz, 3H); 13c NMR (100MHz, CDCl 3) δ 165.99,159.49,143.09,134.63,124.44,122.87,114.55,60.33,55.27,37.71,14.17; IR (film) 2981,1716,1650,1368,1316,1266,1192,1142,1040,976,736; HRMS (ESI) Calcd for C 13h 17o 3s[M+H] +253.0893, Found253.0893.
Embodiment 69
Synthesizing of compound 58:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 58b (1.4mmol, 212.8mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains brown liquid 58 (27.1mg, 64%), R through column chromatography for separation f=0.40 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.30 (d, J=8.8Hz, 2H), 6.77 (d; J=8.8Hz, 2H), 3.72 (s, 3H); 3.48 (t, J=7.0Hz, 2H); 3.41 (d, J=7.0Hz, 2H); 2.93 (t, J=7.0Hz, 2H); 1.11 (t, J=7.0Hz, 3H); 13c NMR (100MHz, CDCl 3) δ 158.95,133.38,125.90,114.49,70.47 – 69.31 (m), 66.30,55.30,35.15,15.13; IR (film) 2972,2866,1592,1493,1462,1284,1244,1176,1103,1031,826; HRMS (EI) Calcd for C 11h 12o 2s212.0871, Found212.0869.
Embodiment 70
Synthesizing of compound 59:
Figure BDA0000465014200000441
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 59b (1.4mmol, 210.0mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains colourless liquid 59 (23.9mg, 57%), R through column chromatography for separation f=0.65 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.29 – 7.23 (m, 2H), 6.80 – 6.74 (m; 2H), 3.72 (s, 3H); 2.77 – 2.71 (m, 2H), 1.56 – 1.48 (m; 2H), 1.33 – 1.26 (m, 2H); 1.25 – 1.17 (m, 2H), 0.81 (t; J=7.2Hz, 3H); 13c NMR (100MHz, CDCl 3) δ 158.73,132.89,127.01,114.49,55.33,35.81,30.88,29.04,22.24,13.94; IR (film) 2959,2927,2856,1495,1462,1262,1243,1095,1034,803; HRMS (ESI) Calcd for C 12h 19oS[M+H] +211.1151, Found211.1154.
Embodiment 71
Synthesizing of compound 60:
Figure BDA0000465014200000442
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), 60b (1.4mmol, 190.4mg), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl L3 (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 2 (0.2mmol, 24.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains colourless liquid 60 (20.8mg, 53%) as a colorless oil, R through column chromatography for separation f=0.60 (PE:EA=20:1); 1h NMR (400MHz, CDCl 3) δ 7.26 (d, J=8.8Hz, 2H), 6.77 (d; J=8.8Hz, 2H), 3.72 (s; 3H), 2.79 – 2.70 (m, 2H); 1.50 (d, J=4.8Hz, 2H); 1.34 (d, J=7.7Hz, 2H); 0.82 (t, J=7.3Hz, 3H); 13c NMR (100MHz, CDCl 3) δ 158.65,32.87,126.86,114.43,55.29,35.46,31.40,21.81,13.64; IR (film) 2957,2927,2870,1592,1492,1461,1283,1243,1175,1033,824.
Embodiment 72
Synthesizing of compound 61:
Figure BDA0000465014200000451
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.1mmol, 24.9mg), 2,2 '-dipyridyl (0.1mmol, 15.6mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 61a (0.2mmol, 34.4mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 24 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 61 (44.1mg, 79%), R through column chromatography for separation f=0.35 (PE:EA=2:1); 1h NMR (400MHz, Acetone) δ 7.77 (d, J=8.5Hz; 2H), 7.47 (dd, J=11.7; 8.0Hz, 4H), 7.33 (t; J=7.4Hz, 2H), 7.27 (d; J=7.2Hz, 1H), 6.57 (s; 2H), 4.35 (s, 2H); 13c NMR (100MHz, Acetone) δ 143.49,141.92,137.73,129.78,129.41,128.21,127.92,127.38,37.05; IR (neat) 3348,3261,1576,1535,1478,1393,1293,1157,1077,902,815,751,719,694.HRMS (EI) Calcd for C 13h 13nO 2s 2279.0388, Found279.0389.
Embodiment 73
Synthesizing of compound 62:
Figure BDA0000465014200000452
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.1mmol, 24.9mg), 2,2 '-dipyridyl (0.1mmol, 15.6mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 62a (0.2mmol, 50.6mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 24 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 62 (56.9mg, 79%), R through column chromatography for separation f=0.25 (PE:EA=2:1); 1h NMR (400MHz, DMSO) δ 11.44 (s, 1H), 7.73 (d; J=8.4Hz, 2H), 7.50 (d, J=8.5Hz; 2H), 7.41 (d, J=7.3Hz, 2H); 7.31 (t, J=7.3Hz, 2H), 7.25 (d; J=7.2Hz, 1H), 6.13 (s, 1H); 4.35 (s, 2H), 2.28 (s, 3H); 13c NMR (100MHz, DMSO) δ 170.44,157.55,144.38,136.43,135.64,128.95,128.60,127.42,127.23,126.59,95.44,35.10,12.11; IR (neat) 3088,2904,2852,1613,1463,1399,1342,1261,1168,1075,1031,930,798,757,718,681; HRMS (ESI) Calcd for C 17h 17n 2o 3s 2[M+H] +361.0675, Found361.0670.
Embodiment 74
Synthesizing of compound 63:
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μl), CuSO 45H 2o (0.1mmol, 24.9mg), 2,2 '-dipyridyl (0.1mmol, 15.6mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 63a (0.2mmol, 50.0mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 24 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 63 (55.0mg, 77%), R through column chromatography for separation f=0.15 (PE:EA=2:1); 1h NMR (400MHz, DMSO) δ 11.81 (s, 1H), 8.49 (d, J=4.9Hz; 2H), 7.84 (d, J=8.5Hz, 2H), 7.48 (d; J=8.6Hz, 2H), 7.39 (d, J=7.1Hz; 2H), 7.30 (t, J=7.3Hz, 2H); 7.25 (d, J=7.2Hz, 1H), 7.05 (t; J=4.9Hz, 1H), 4.34 (s, 2H); 13c NMR (100MHz, DMSO) δ 158.41,156.87,143.58,136.70,136.51,128.94,128.55,128.04,127.36,126.26,115.83,35.19; IR (neat) 3379,3039,2732,1582,1501,1453,1413,1336,1155,1100,953,799,749,717; HRMS (ESI) Calcd for C 17h 16n 3o 2s 2[M+H] +358.0678, Found358.0677.
Embodiment 75
Synthesizing of compound 64:
Figure BDA0000465014200000471
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 347.5mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 5.1mg), 2,2 '-dipyridyl (0.02mmol, 3.1mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 64a (0.2mmol, 51.8mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 64 (65.8mg, 93%), R through column chromatography for separation f=0.5 (PE:EA=1:2); 1h NMR (400MHz, CDCl 3) δ 8.13 (s, 1H), 7.68 (d, J=7.4Hz; 1H), 7.47 (d, J=7.3Hz, 1H); 7.38 (t, J=7.6Hz, 1H), 7.21 – 7.14 (m; 3H), 7.14 – 7.07 (m, 2H), 5.11 (dd; J=13.3,5.2Hz, 1H), 4.15 (d; J=16.6Hz, 1H), 4.08 – 3.98 (m; 2H), 3.84 (d, J=16.6Hz; 1H), 2.87 – 2.72 (m, 2H); 2.19 (dd, J=13.1,5.0Hz; 1H), 2.10 – 2.01 (m, 1H); 13c NMR (100MHz, CDCl 3) δ 171.10,169.30,168.95,143.12,137.09,134.04,131.77,131.03,129.20,128.70,128.57,127.46,122.64,51.65,46.59,39.09,31.49,23.30; IR (film) 3199,3100,2923,1687,1198,1144,804,743.HRMS (EI) Calcd for C 20h 18n 2o 3s366.1038, Found366.1040.
Embodiment 76
Synthesizing of compound 65:
Figure BDA0000465014200000472
In reaction tubes, add Na 2s 2o 35H 2o (0.7mmol, 185.3mg), BnCl (0.7mmol, 81 μ L), CuSO 45H 2o (0.05mmol, 14.1mg), 2,2 '-dipyridyl (0.05mmol, 7.9mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 65a (0.2mmol, 51.8mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 65 (29.3mg, 73%) as a white solid, R through column chromatography for separation f=0.7 (PE:EA=2:1); 1h NMR (400MHz, CDCl 3) δ 7.20 (td, J=6.1,1.4Hz, 5H), 7.15 (d; J=8.1Hz, 2H), 6.94 (d, J=8.0Hz, 2H); 4.89 (d, J=8.0Hz, 1H), 4.49 (d; J=8.0Hz, 1H), 4.02 (s, 2H); 3.63 (s, 3H), 2.96 (dd, J=14.0; 5.9Hz, 2H), 1.35 (s, 9H); 13c NMR (100MHz, CDCl 3) δ 172.18,155.00,137.30,134.86,134.24,130.04,129.74,128.79,128.45,127.15,79.97,54.25,52.24,39.07,37.82,28.26; IR (film) 3367,2977,1744,1712,1494,1365,1163,1017,699.HRMS (EI) Calcd for C 22h 27nO 4s401.1661, Found401.1657.
Embodiment 77
Synthesizing of compound 66:
Figure BDA0000465014200000481
In reaction tubes, add Na 2s 2o 35H 2o (1.4mmol, 360.0mg), BnCl (1.4mmol, 161 μ L), CuSO 45H 2o (0.02mmol, 6.1mg), 2,2 '-dipyridyl (0.02mmol, 3.6mg), methanol/water (1mL/1mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 66a (0.1mmol, 62.7mg), nitrite tert-butyl (0.3mmol, 40 μ L), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, under room temperature condition, in system, add ethyl acetate (10mL), anhydrous magnesium sulfate drying, filters, concentrated, obtains white solid 66 (57.1mg, 78%), R through column chromatography for separation f=0.5 (PE:EA=2:1); 1h NMR (400MHz, CDCl 3) δ 7.91 (ddd, J=14.6,10.9,7.8Hz; 6H), 7.72 – 7.67 (m, 2H), 7.50 – 7.41 (m; 2H), 7.38 – 7.30 (m, 6H), 7.28 – 7.23 (m; 4H), 7.16 (q, J=7.6Hz, 4H); 5.92 (t, J=7.1Hz, 2H); 5.58 (dd, J=10.1,3.6Hz; 1H), 5.24 (d, J=3.6Hz; 1H), 4.51 (s, 2H); 4.36 – 4.28 (m, 1H), 4.16 (s; 2H), 3.41 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 166.06,166.02,165.47,165.21,144.82,136.21; 133.35,133.19,133.11,130.22,129.84; 129.67,129.65,129.48,129.15,129.12; 128.71,128.42,128.40,128.23,127.53; 126.86,125.90,97.56,69.33,69.17; 68.28,66.77,62.59,55.68,37.13; IR (film) 3479,3380,1716,1624,1602,1260,1171,1093,1069,1028,708; HRMS (ESI) Calcd for C 42h 40nO 10s[M+H] +750.2367, Found750.2355.
Embodiment 78
Synthesizing of benzyl (4-p-methoxy-phenyl) thioether:
Figure BDA0000465014200000491
In 100mL round-bottomed flask, add Na 2s 2o 35H 2o (70mmol, 17.386g), BnCl (70mmol, 8.0mL), CuSO 45H 2o (1.0mmol, 251.7mg), 2,2 '-dipyridyl L3 (1.0mmol, 157.5mg), methanol/water (25mL/25mL), reaction system stirs 2 hours at 80 ℃; Afterwards, reaction system is cooled to 0 ℃, adds substrate 1 (10mmol, 1.230g), nitrite tert-butyl (15mmol, 1.8mL), reaction system, under 80 ℃ of conditions, stirs 4.5 hours.Monitoring reaction process.After completion of the reaction, in system, add ethyl acetate (20mL), separatory, ethyl acetate (2*20mL) aqueous phase extracted, set organic phase, anhydrous magnesium sulfate drying, filters, concentrated, obtain target product 2 (2.30g, 99%) through column chromatography for separation.
Embodiment 79
Synthesizing of benzyl (4-p-methoxy-phenyl) sulfoxide
Figure BDA0000465014200000492
In reaction tubes, add compound 2 (46mg, 0.2mmol), methanol/water (0.5mL/0.5mL) afterwards, adds NaIO in batches 4(64.2mg, 0.3mmol), under reaction system room temperature condition, stir 2 hours, after completion of the reaction, saturated sodium thiosulfate solution cancellation reaction, ethyl acetate (3*5mL) aqueous phase extracted, set organic phase, anhydrous magnesium sulfate drying, filter, concentrated, obtain target product 67 (39.8mg, 81%) through column chromatography for separation. 1H?NMR(400MHz,CDCl 3)δ7.30(dd,J=17.2,8.0Hz,5H),6.99(d,J=6.6Hz,2H),6.94(d,J=8.5Hz,2H),4.12(d,J=12.4Hz,1H),3.97(d,J=12.4Hz,1H),3.85(s,3H); 13C?NMR(100MHz,CDCl 3)δ161.97,133.51,130.33,129.20,128.39,128.10,126.28,114.28,63.67,55.44;IR(film)3087,3063,3030,2925,2854,1596,1495,1455,1252,1034,765,740,700.
Embodiment 80
Synthesizing of benzyl (4-p-methoxy-phenyl) sulfone
Figure BDA0000465014200000501
In reaction tubes, add compound 2 (46mg, 0.2mmol), methylene dichloride (2mL), under 0 ℃ of condition, add mCPBA (103.2mg in batches, 2.0mmol), under reaction system room temperature condition, stir 10 hours, after completion of the reaction, saturated sodium thiosulfate solution cancellation reaction, ethyl acetate (3*10mL) aqueous phase extracted, set organic phase, anhydrous magnesium sulfate drying, filter, concentrated, obtain target product 68 (43.0mg, 85%) through column chromatography for separation. 1H?NMR(400MHz,CDCl 3)δ7.45(d,J=8.9Hz,2H),7.24(d,J=7.1Hz,1H),7.20(t,J=7.2Hz,2H),7.01(d,J=7.0Hz,2H),6.82(d,J=8.9Hz,2H),4.22(s,2H),3.79(s,3H). 13C?NMR(100MHz,CDCl 3)δ163.66,130.78(d,J=1.0Hz),129.31,128.64,128.51,128.43,113.98,63.06,55.61;IR(film)3062,2944,2838,1699,1595,1680,1493,1457,1408,1311,1294,1248,1145,1089,1029,774,695。

Claims (10)

1. a synthetic method for arylalkyl sulfide compound, is characterized in that, take aryl amine derivatives and halogenated alkane as reaction raw materials, with Na 2s 2o 3for sulfuration reagent, under copper catalyst effect, in reaction solvent, react and obtain suc as formula the arylalkyl sulfide compound shown in (II); Described reaction process is as shown in reaction formula;
Figure FDA0000465014190000011
Wherein, Ar is phenyl ring, heterocycle, substituted benzene ring or substituted heterocycle;
R is straight chained alkyl, branched paraffin or contains aromatic yl paraffin;
X is I, Br or Cl;
R ' is straight chained alkyl, branched paraffin or contains aromatic yl paraffin.
2. the synthetic method of arylalkyl sulfide compound as claimed in claim 1, is characterized in that, described copper catalyst is CuSO 4, CuSO 45H 2o, Cu (OAc) 2, Cu (NO 3) 2, Cu (TFA) 2, Cu (OTf) 2, CuCl 2, CuBr 2, Cu (acac) 2, CuO, CuOAc, CuI, CuBr, CuCl, CuTc, or Cu; The consumption of described copper catalyst is 1-80%.
3. the synthetic method of arylalkyl sulfide compound as claimed in claim 1, is characterized in that, described part is PPh 3, P tbu 3, tricyclohexyl phosphine, three furyl phosphines, 1, two (diphenylphosphine) methane of 1-, 1, two (diphenylphosphine) ethane of 2-, 1, two (diphenylphosphine) propane of 3-, 1, two (diphenyl phosphine) butane of 4-, 1, 1 '-bis-(diphenylphosphine) ferrocene, 2 '-bis-diphenyl phosphine-1, 1 '-dinaphthalene, pyridine, 2, 2 '-dipyridyl, 4, 4 '-dimethyl-2, 2 '-dipyridyl, 4, 4 '-dipyridyl, 4, 4 '-di-t-butyl-2, 2 '-dipyridyl, 1, 10 ' luxuriant and rich with fragrance sound of vomiting quinoline, 2, 9-dimethyl-4, 7-biphenyl-1, 10-phenanthrolene, or 4, 7-phenylbenzene-1, the luxuriant and rich with fragrance sound of vomiting of 10-quinoline, described part consumption is 1-80%.
4. the synthetic method of arylalkyl sulfide compound as claimed in claim 1, it is characterized in that, described solvent is methyl alcohol, ethanol, Virahol, the trimethyl carbinol, water, DMSO, DMF, DMA, acetonitrile, acetone, tetrahydrofuran (THF), toluene, methylene dichloride, 1, any one of 2-ethylene dichloride, chloroform or arbitrary combination.
5. the synthetic method of arylalkyl sulfide compound as claimed in claim 1, is characterized in that, in described reaction, and raw material aryl amine derivatives and described sulfuration reagent N a 2s 2o 3usage ratio be 1: 1-1: 15.
6. the synthetic method of arylalkyl sulfide compound as claimed in claim 1, is characterized in that, in described reaction, the usage ratio of raw material aryl amine derivatives and described halogenated alkane is 1: 1-1: 15.
7. the synthetic method of arylalkyl sulfide compound as claimed in claim 1, is characterized in that, described reaction comprises the following steps:
(1) in reaction vessel, add sulfuration reagent, halogenated alkane, copper catalyst, solvent, stirring reaction under 0-100 ℃ of condition; (2) reaction system step (1) being obtained is cooled to 0 ℃, add aryl amine derivatives substrate, the alkyl nitriteester shown in formula (I), stirring reaction under 0-100 ℃ of condition, obtains the arylalkyl sulfide compound shown in formula (II).
8. the synthetic method of arylalkyl sulfide compound as claimed in claim 7, is characterized in that, described step (1) is carried out under 80 ℃ of conditions; Described step (2) is carried out under room temperature to 80 ℃ condition.
9. the arylalkyl sulfide compound preparing by synthetic method described in claim 1, is characterized in that, its structure is suc as formula shown in (II),
Figure FDA0000465014190000021
Wherein, Ar is phenyl ring, heterocycle, substituted benzene ring or substituted heterocycle; R is straight chained alkyl, branched paraffin or contains aromatic yl paraffin.
10. an arylalkyl sulfide compound, is characterized in that, its structure is suc as formula shown in (II):
Figure FDA0000465014190000022
Wherein, Ar is 2-iodophenyl, 2-isopropyl phenyl, 2-chloro-4 nitrophenyl, 2-methyl-formiate-5-chloro-phenyl-, 3-chloro-phenyl-, 3-nitrophenyl, 3-nitro-4-methyl phenyl, 3-nitro-4-chloro-phenyl-, 3, 4, 5-trimethoxyphenyl, 3, 5-dioctyl phthalate methyl esters phenyl, 4-thiomethyl phenyl, 4-acetonitrile phenyl, 4-ethyl formate phenyl, 2-methyl-4-nitrophenyl, 4-carboxyl phenyl, 3-methane amide phenyl, 4-azobenzene phenyl, the trimethyl silicon based ethynyl phenyl of 4-, 4-ethynyl phenyl, pyridine, indoles, benzo lactone, fluorenes, 4-sulfanilamide (SN) phenyl, 4-replaces sulfanilamide (SN) phenyl, replace benzo lactan, amino acid derivative, sugar derivatives, R is 2,6-benzyl dichloride chlorine, 2,6-bis-trifluoromethyl benzyl chlorine, 4-fluorine benzyl chlorine, 4-bromobenzyl chlorine, 4-trifluoromethyl benzyl chlorine, 4-nitrobenzyl chlorine, substituted allyl, ether, n-pentyl.
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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104045589A (en) * 2014-05-07 2014-09-17 华东师范大学 Aryl alkyl thioether compound and synthetic method thereof
CN104725172A (en) * 2015-02-26 2015-06-24 华东师范大学 Synthetic method of aryl sulfide type compound
CN105218418A (en) * 2015-10-01 2016-01-06 宜春学院 A kind of preparation method of thioether
WO2017215110A1 (en) * 2016-06-15 2017-12-21 苏州大学 Synthetic method for asymmetrical thioether
CN110117240A (en) * 2018-02-07 2019-08-13 华东师范大学 Thiamine disulfide class compound and its synthetic method and application
WO2019196812A1 (en) * 2018-04-09 2019-10-17 上海科技大学 Protein degradation targeting compound, anti-tumor application, intermediate thereof and use of intermediate
CN111606883A (en) * 2019-02-25 2020-09-01 上海科技大学 Sulfur-containing compound based on glutarimide framework and application thereof
CN112010722A (en) * 2020-09-14 2020-12-01 南通大学 Synthesis method of E-type beta-thiocyanatelamide derivative
CN113563235A (en) * 2021-07-28 2021-10-29 上海毕得医药科技股份有限公司 Synthetic method of 3- (halogenated phenoxy) benzenesulfonyl chloride derivative

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1261071A (en) * 1999-01-19 2000-07-26 金湖石油化学株式会社 Matte salts and production thereof
CN1434030A (en) * 2003-02-14 2003-08-06 武汉大学 2,5-dimethoxy ethyl phenyl sulfide and synthesis method and use thereof
CN1434029A (en) * 2003-02-14 2003-08-06 武汉大学 2,5-dimethoxy-4-ethyl benzaldehyde sulfide and preparation process and use thereof
CN101031543A (en) * 2004-09-29 2007-09-05 西巴特殊化学品控股有限公司 Process for preparing aromatic thiophenyl ketones

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1261071A (en) * 1999-01-19 2000-07-26 金湖石油化学株式会社 Matte salts and production thereof
CN1434030A (en) * 2003-02-14 2003-08-06 武汉大学 2,5-dimethoxy ethyl phenyl sulfide and synthesis method and use thereof
CN1434029A (en) * 2003-02-14 2003-08-06 武汉大学 2,5-dimethoxy-4-ethyl benzaldehyde sulfide and preparation process and use thereof
CN101031543A (en) * 2004-09-29 2007-09-05 西巴特殊化学品控股有限公司 Process for preparing aromatic thiophenyl ketones

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ACS: "STN AN 2009:643329", 《STN CAPLUS》, 28 May 2009 (2009-05-28), pages 1 - 4 *

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104045589A (en) * 2014-05-07 2014-09-17 华东师范大学 Aryl alkyl thioether compound and synthetic method thereof
CN104045589B (en) * 2014-05-07 2016-08-24 华东师范大学 A kind of arylalkyl thioethers compound and synthetic method thereof
CN104725172A (en) * 2015-02-26 2015-06-24 华东师范大学 Synthetic method of aryl sulfide type compound
CN104725172B (en) * 2015-02-26 2017-03-01 华东师范大学 A kind of synthetic method of aryl thioethers class compound
CN105218418A (en) * 2015-10-01 2016-01-06 宜春学院 A kind of preparation method of thioether
WO2017215110A1 (en) * 2016-06-15 2017-12-21 苏州大学 Synthetic method for asymmetrical thioether
US10112896B2 (en) 2016-06-15 2018-10-30 Soochow University Method for synthesizing dissymmetric sulfoether
CN110117240A (en) * 2018-02-07 2019-08-13 华东师范大学 Thiamine disulfide class compound and its synthetic method and application
WO2019196812A1 (en) * 2018-04-09 2019-10-17 上海科技大学 Protein degradation targeting compound, anti-tumor application, intermediate thereof and use of intermediate
CN110357889A (en) * 2018-04-09 2019-10-22 上海科技大学 Protein degradation target compound, its antitumor application thereof, wherein mesosome and intermediate application
CN110357889B (en) * 2018-04-09 2022-03-15 上海科技大学 Protein degradation targeting compound, anti-tumor application thereof, intermediate thereof and application of intermediate
JP7367908B2 (en) 2018-04-09 2023-10-24 上海科技大学 Targeted proteolytic compounds, their antitumor applications, their intermediates and applications of intermediates
KR102548191B1 (en) 2018-04-09 2023-06-28 상하이테크 유니버시티 Targeted proteolytic compounds, their antitumor applications, their intermediates and applications of intermediates
KR20210006364A (en) * 2018-04-09 2021-01-18 상하이테크 유니버시티 Target proteolytic compounds, their anti-tumor applications, their intermediates and applications of intermediates
JP2021521163A (en) * 2018-04-09 2021-08-26 上海科技大学Ｓｈａｎｇｈａｉ Ｔｅｃｈ Ｕｎｉｖｅｒｓｉｔｙ Target proteolytic compounds, their antitumor applications, their intermediates and their applications
AU2019251151B2 (en) * 2018-04-09 2022-07-07 Shanghaitech University Target protein degradation compounds, their anti-tumor use, their intermediates and use of intermediates
CN111606883A (en) * 2019-02-25 2020-09-01 上海科技大学 Sulfur-containing compound based on glutarimide framework and application thereof
JP2022521746A (en) * 2019-02-25 2022-04-12 上海科技大学 Sulfur-containing compounds based on glutarimide skeleton and their applications
CN111606883B (en) * 2019-02-25 2023-05-09 上海科技大学 Sulfur-containing compound based on glutarimide skeleton and application thereof
WO2020173426A1 (en) * 2019-02-25 2020-09-03 上海科技大学 Sulfur-containing compound based on glutarimide skeleton and application thereof
CN112010722B (en) * 2020-09-14 2023-01-06 南通大学 Synthesis method of E-type beta-thiocyanatelamide derivative
CN112010722A (en) * 2020-09-14 2020-12-01 南通大学 Synthesis method of E-type beta-thiocyanatelamide derivative
CN113563235A (en) * 2021-07-28 2021-10-29 上海毕得医药科技股份有限公司 Synthetic method of 3- (halogenated phenoxy) benzenesulfonyl chloride derivative

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