CN113816815B - Synthesis method of 1-thiophenyl-2-aromatic phenolic compound - Google Patents
Synthesis method of 1-thiophenyl-2-aromatic phenolic compound Download PDFInfo
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- 238000001308 synthesis method Methods 0.000 title claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 72
- 238000010438 heat treatment Methods 0.000 claims abstract description 21
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical class SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 9
- 239000000376 reactant Substances 0.000 claims abstract description 8
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 195
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 50
- 238000001035 drying Methods 0.000 claims description 34
- 239000003208 petroleum Substances 0.000 claims description 25
- 238000003756 stirring Methods 0.000 claims description 24
- 238000004809 thin layer chromatography Methods 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 21
- 238000004440 column chromatography Methods 0.000 claims description 20
- 239000003480 eluent Substances 0.000 claims description 20
- 238000001914 filtration Methods 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 19
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 19
- 230000002194 synthesizing effect Effects 0.000 claims description 16
- 230000035484 reaction time Effects 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 238000000926 separation method Methods 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 238000013375 chromatographic separation Methods 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 239000007800 oxidant agent Substances 0.000 abstract description 3
- 230000001590 oxidative effect Effects 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 238000006561 solvent free reaction Methods 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 30
- 238000001816 cooling Methods 0.000 description 28
- 239000012043 crude product Substances 0.000 description 26
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 20
- 150000001875 compounds Chemical class 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 17
- 238000012544 monitoring process Methods 0.000 description 16
- 239000002904 solvent Substances 0.000 description 14
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 description 10
- 229950011260 betanaphthol Drugs 0.000 description 10
- 239000003814 drug Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- -1 thiophenol free radical Chemical class 0.000 description 7
- 238000004090 dissolution Methods 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- BXYUFYNRKAGWIJ-UHFFFAOYSA-N 1-(4-bromophenyl)sulfanylnaphthalen-2-ol Chemical compound BrC1=CC=C(C=C1)SC1=C(C=CC2=CC=CC=C12)O BXYUFYNRKAGWIJ-UHFFFAOYSA-N 0.000 description 1
- NESVMNMXOXTBDG-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfanylnaphthalen-2-ol Chemical compound Oc1ccc2ccccc2c1Sc1ccc(Cl)cc1 NESVMNMXOXTBDG-UHFFFAOYSA-N 0.000 description 1
- BZNGNIBFCUNILP-UHFFFAOYSA-N 1-(4-fluorophenyl)sulfanylnaphthalen-2-ol Chemical compound Oc1ccc2ccccc2c1Sc1ccc(F)cc1 BZNGNIBFCUNILP-UHFFFAOYSA-N 0.000 description 1
- PNQZTJCBTHQACL-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonylnaphthalen-2-ol Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C1=C(O)C=CC2=CC=CC=C12 PNQZTJCBTHQACL-UHFFFAOYSA-N 0.000 description 1
- XFGHBTJJVSNRLL-UHFFFAOYSA-N 1-(4-nitrophenyl)sulfanylnaphthalen-2-ol Chemical compound Oc1ccc2ccccc2c1Sc1ccc(cc1)[N+]([O-])=O XFGHBTJJVSNRLL-UHFFFAOYSA-N 0.000 description 1
- BIJNHUAPTJVVNQ-UHFFFAOYSA-N 1-Hydroxypyrene Chemical compound C1=C2C(O)=CC=C(C=C3)C2=C2C3=CC=CC2=C1 BIJNHUAPTJVVNQ-UHFFFAOYSA-N 0.000 description 1
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- BICHBFCGCJNCAT-UHFFFAOYSA-N 2,4-difluorobenzenethiol Chemical compound FC1=CC=C(S)C(F)=C1 BICHBFCGCJNCAT-UHFFFAOYSA-N 0.000 description 1
- PWOBDMNCYMQTCE-UHFFFAOYSA-N 2-chlorobenzenethiol Chemical compound SC1=CC=CC=C1Cl PWOBDMNCYMQTCE-UHFFFAOYSA-N 0.000 description 1
- CQJDYPZUDYXHLM-UHFFFAOYSA-N 3-chlorobenzenethiol Chemical compound SC1=CC=CC(Cl)=C1 CQJDYPZUDYXHLM-UHFFFAOYSA-N 0.000 description 1
- FTBCOQFMQSTCQQ-UHFFFAOYSA-N 4-bromobenzenethiol Chemical compound SC1=CC=C(Br)C=C1 FTBCOQFMQSTCQQ-UHFFFAOYSA-N 0.000 description 1
- OSDLLIBGSJNGJE-UHFFFAOYSA-N 4-chloro-3,5-dimethylphenol Chemical compound CC1=CC(O)=CC(C)=C1Cl OSDLLIBGSJNGJE-UHFFFAOYSA-N 0.000 description 1
- YLDFTMJPQJXGSS-UHFFFAOYSA-N 6-bromo-2-naphthol Chemical compound C1=C(Br)C=CC2=CC(O)=CC=C21 YLDFTMJPQJXGSS-UHFFFAOYSA-N 0.000 description 1
- WKTNIBWKHNIPQR-UHFFFAOYSA-N 6-hydroxynaphthalene-2-carbonitrile Chemical compound C1=C(C#N)C=CC2=CC(O)=CC=C21 WKTNIBWKHNIPQR-UHFFFAOYSA-N 0.000 description 1
- JVYALCZIBSRZFE-UHFFFAOYSA-N BrC=1C=C2C=CC(=C(C2=CC=1)SC1=CC=C(C=C1)Cl)O Chemical compound BrC=1C=C2C=CC(=C(C2=CC=1)SC1=CC=C(C=C1)Cl)O JVYALCZIBSRZFE-UHFFFAOYSA-N 0.000 description 1
- AHVQGDQGJOOZIH-UHFFFAOYSA-N CC(C=C1C)=CC(O)=C1SC(C=C1)=CC=C1Cl Chemical compound CC(C=C1C)=CC(O)=C1SC(C=C1)=CC=C1Cl AHVQGDQGJOOZIH-UHFFFAOYSA-N 0.000 description 1
- JAKZDERJMQXRQP-UHFFFAOYSA-N CC(C=C1C=C2)=CC=C1C(SC(C=C1)=CC=C1Cl)=C2O Chemical compound CC(C=C1C=C2)=CC=C1C(SC(C=C1)=CC=C1Cl)=C2O JAKZDERJMQXRQP-UHFFFAOYSA-N 0.000 description 1
- SKKIMURYPKODKJ-UHFFFAOYSA-N ClC1=C(C=CC=C1)SC1=C(C=CC2=CC=CC=C12)O Chemical compound ClC1=C(C=CC=C1)SC1=C(C=CC2=CC=CC=C12)O SKKIMURYPKODKJ-UHFFFAOYSA-N 0.000 description 1
- QYCNFZWFRAGFMH-UHFFFAOYSA-N ClC1=CC=C(C=C1)SC1=C(C2=CC=C3C=CC=C4C=CC(=C1)C2=C43)O Chemical compound ClC1=CC=C(C=C1)SC1=C(C2=CC=C3C=CC=C4C=CC(=C1)C2=C43)O QYCNFZWFRAGFMH-UHFFFAOYSA-N 0.000 description 1
- GXBWNMOYJATRSQ-UHFFFAOYSA-N ClC1=CC=C(C=C1)SC1=C2C=CC(=CC2=CC=C1O)C#N Chemical compound ClC1=CC=C(C=C1)SC1=C2C=CC(=CC2=CC=C1O)C#N GXBWNMOYJATRSQ-UHFFFAOYSA-N 0.000 description 1
- QCUALDXPHKDFDD-UHFFFAOYSA-N ClC=1C=C(C=CC=1)SC1=C(C=CC2=CC=CC=C12)O Chemical compound ClC=1C=C(C=CC=1)SC1=C(C=CC2=CC=CC=C12)O QCUALDXPHKDFDD-UHFFFAOYSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- JQDFFUBXQHWWBJ-UHFFFAOYSA-N FC=1C=C(C=CC=1)SC1=C(C=CC2=CC=CC=C12)O Chemical compound FC=1C=C(C=CC=1)SC1=C(C=CC2=CC=CC=C12)O JQDFFUBXQHWWBJ-UHFFFAOYSA-N 0.000 description 1
- MCPHYROKIKIFAT-UHFFFAOYSA-N OC(C=CC1=CC=CC=C11)=C1C(C=CC(SF)=C1)=C1SF Chemical compound OC(C=CC1=CC=CC=C11)=C1C(C=CC(SF)=C1)=C1SF MCPHYROKIKIFAT-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000000498 cooling water Substances 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B45/00—Formation or introduction of functional groups containing sulfur
- C07B45/06—Formation or introduction of functional groups containing sulfur of mercapto or sulfide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/64—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method of a 1-thiophenyl-2-aromatic phenol compound, which comprises the step of heating and reacting a first reactant and a thiophenol derivative under an alkaline condition in an air environment to prepare the 1-thiophenyl-2-aromatic phenol compound. The synthesis method of the invention provides a brand-new, simple and efficient synthesis way for the 1-thiophenyl-2-aromatic phenol compound, has good industrial prospect and potential application value, and has the following beneficial effects: the high-selectivity synthesis of the monosulfide product, the source of the oxidant is air, the green solvent-free reaction is realized, the reaction energy is amplified, and the effect is still very good.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of a 1-thiophenyl-2-aromatic phenol compound.
Background
Sulfur is widely present in commercial drugs, natural products and some basic materials, so that the construction of carbon-sulfur bonds is very important in organic synthesis. The construction of the C-S bond is usually achieved by a cross-coupling reaction of an aryl halide with a thiol or disulfide catalyzed by a transition metal, and these synthetic methods often require expensive transition metal catalysts, organic solvents, and stoichiometric amounts of oxidizing agents.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a synthesis method of a 1-thiophenyl-2-aromatic phenolic compound, which has the advantages of cheap and easily-obtained reaction substrate, simple and convenient operation, short reaction time, low production cost, less pollution, simple post-treatment, single reaction product and higher reaction yield, and particularly has the oxidant source of only air, thereby being an ideal oxidation source which is environment-friendly and extremely popular with people.
The purpose of the invention is realized by the following technical scheme.
A method for synthesizing 1-thiophenyl-2-aromatic phenolic compounds comprises the following steps:
in the air environment, a first reactant, a thiophenol derivative and alkali are stirred and reacted under the heating condition, extraction, filtration and column chromatography separation are carried out, and a 1-thiophenyl-2-aromatic phenol compound is obtained, wherein the ratio of the first reactant, the thiophenol derivative and the alkali is (1-3): (0.5-1.0), wherein the base is potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, potassium hydroxide, sodium hydroxide, potassium tert-butoxide, lithium tert-butoxide or Diazabicyclo (DBU).
In the above technical solution, the first reactant is: 
Wherein R is 1 H, Br or CN.
In the technical scheme, the thiophenol derivative is
Wherein R is 2 Is Cl, Br, F, Me or NO 2 。
In the technical scheme, the stirring reaction temperature is 40-120 ℃.
In the technical scheme, the time for stirring the reaction is determined by adopting thin layer chromatography.
In the above technical scheme, the stirring reaction time is at least 30min, preferably 30min to 4 h.
In the technical scheme, the eluent used for column chromatography separation is a mixture of ethyl acetate and petroleum ether, and the ratio of the ethyl acetate to the petroleum ether is (30-50) according to volume parts.
In the technical scheme, the extraction is to add ethyl acetate and water.
In the above technical scheme, drying is carried out by using anhydrous sodium sulfate before filtration.
The synthesis method of the invention provides a brand-new, simple and efficient synthesis way for the 1-thiophenyl-2-aromatic phenol compound, has good industrial prospect and potential application value, and has the following beneficial effects:
1. high selectivity synthesis of monosulfide.
2. Green and solvent-free reaction.
3. The reaction energy is amplified and the effect is still very good.
Detailed Description
The technical scheme of the invention is further explained by combining specific examples.
In the specific implementation mode of the invention, the reagents and medicines involved in the synthesis are purchased from Tianjin reagent six factories in commercial way, the purity of the medicines is analytically pure, and the reagents and the medicines are directly used without any pretreatment.
The synthesis method of the invention continuously stirs in the whole process, and the model of an electromagnetic heating stirrer used for stirring is NUOVAII (Temaran, USA); the rotary evaporator was model RE-2000A (Otsuwa instruments liability Co., Ltd., Otsu). Nuclear magnetic resonance instrument model: bruker AV-400spectrometer, 400MHz, DMSO-d 6.
In the invention, the reaction is carried out under the condition of heating to 40-120 ℃, and the degree of the reaction progress is detected by Thin Layer Chromatography (TLC). In thin layer chromatography, silica gel plate type G254 with size of 15mm × 50mm is used; the developing solvent is a mixture of ethyl acetate and petroleum ether, and the volume ratio of the ethyl acetate to the petroleum ether is 1:15
The eluent used for column chromatography separation in the following examples is a mixture of ethyl acetate and petroleum ether, and the ratio of ethyl acetate to petroleum ether is 1:30 by volume.
The detection process uses a ZF-I type three-purpose ultraviolet analyzer (Shanghai Ching Tang), the used medicines are purchased from Tianjin reagent six factories, the purity of the medicines is analytical purity, all medicines are directly used, and no pretreatment is carried out. When TLC detection shows that the first reactant of the raw material disappears and the target product point does not change any more, the synthesis method of the invention is marked to end the reaction, and the next separation operation can be continued.
The temperature of the cooling water in the following examples was 20 ℃.
The following examples were all carried out in air.
The reaction principle of the synthetic method of the invention is as follows: firstly, oxidizing thiophenol derivatives by oxygen in the air under the alkaline condition to generate peroxysulfide, further generating thiophenol free radicals, and simultaneously generating only a byproduct water (a); phenol can generate three free radical tautomers (b) under the action of thiophenol free radical; combining thiophenol free radical with stable phenol free radical, and tautomerizing to obtain final product (c)
Example 1
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (1- (p-chlorophenylthio) -2-naphthol) comprises the following steps:
sequentially adding 0.6mmol (0.0864g) of 2-naphthol, 1.8mmol (0.259g) of p-chlorothiophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, heating and stirring the flask in the air at 80 ℃, monitoring the reaction by TLC (the reaction time is 1.5h), cooling the flask to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate for dissolving, then adding 15ml of cold water for cooling, extracting the solution twice by using 20ml of ethyl acetate, drying the organic phase by anhydrous sodium sulfate, filtering and distilling the solution, separating and purifying the product by column chromatography, and drying the product by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C) 16 H 11 ClOS)0.266g, purity greater than 99%, reaction yield 93%.
1H NMR(400MHz,DMSO-d6):δ6.94(d,2H,ArH,J＝8.4Hz),7.25(d,2H,ArH,J＝8.4Hz),7.33-7.38(m,2H,ArH),7.50(t,1H,ArH,J＝7.8Hz),7.89(d,1H,ArH,J＝8Hz),7.98(d,1H,ArH,J＝8.8Hz),8.17(d,1H,ArH,J＝8.8Hz),10.39(s,1H,OH).13C NMR(100MHz,DMSO-d6):δ158.9,137.3,136.1,132.8,129.8,129.3,129.0,128.2,127.7,124.2,123.8,118.9,107.4
Example 2
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (1- (p-bromophenylthio) -2-naphthol) comprises the following steps:
sequentially adding 0.6mmol (0.0864g) of 2-naphthol, 1.8mmol (0.334g) of p-bromothiophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, heating and stirring the flask in the air at 80 ℃, monitoring the reaction by TLC (1 h for reaction), cooling the flask to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate for dissolution, adding 15ml of cold water for cooling, extracting the mixture twice by using 20ml of ethyl acetate, drying the organic phase by using anhydrous sodium sulfate, filtering and distilling the solvent, separating and purifying the crude product by column chromatography, and drying the crude product by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C) 16 H 11 BrOS)0.314g, purity more than 99% and reaction yield 95%.
1 H NMR(400MHz,DMSO-d 6 ):δ6.90(d,2H,ArH,J＝8.6Hz),7.34-7.39(m,4H,ArH),7.48-7.52(m,1H,ArH),7.89(d,1H,ArH,J＝8.0Hz),7.98(d,1H,ArH,J＝9.0Hz),8.18(d,1H,ArH,J＝8.4Hz),10.41(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ158.9,138.0,136.1,132.9,132.2,129.1,129.0,128.3,128.1,124.3,123.8,119.0,118.0,107.4.
Example 3
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (1- (p-fluorophenylthio) -2-naphthol) comprises the following steps:
0.6mmol (0.0864g) of 2-naphthol,Adding 1.8mmol (0.230g) of p-fluorobenzothiophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, placing the flask in air, heating at 80 ℃ and stirring for reaction, monitoring the reaction by TLC (reaction time is 1h), cooling to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate for dissolution, then adding 15ml of cold water for cooling, extracting twice with 20ml of ethyl acetate, drying an organic phase with anhydrous sodium sulfate, filtering and distilling off the solvent, separating and purifying a crude product by column chromatography, and drying by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C) 16 H 11 FOS)0.259g, purity more than 99% and reaction yield 96%.
1 H NMR(400MHz,DMSO-d 6 ):δ7.00-7.08(m,4H,ArH),7.34-7.37(m,2H,ArH),7.49-7.52(m,1H,ArH),7.88(d,1H,ArH,J＝8.0Hz),7.97(d,1H,ArH,J＝8.0Hz),8.24(d,1H,ArH,J＝8.0Hz),10.33(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ161.8,159.4,158.8,136.2,133.6,132.7,129.1,129.0,128.5,128.4,123.7,119.0,116.6,108.6.
Example 4
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (1- (p-toluenesulfonyl) -2-naphthol) comprises the following steps:
sequentially adding 0.6mmol (0.0864g) of 2-naphthol, 1.8mmol (0.223g) of p-toluenesulfophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, placing the flask in the air, heating and stirring at 80 ℃, monitoring the reaction by TLC (1 h for reaction), cooling to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate for dissolution, then adding 15ml of cold water for cooling, extracting twice by using 20ml of ethyl acetate, drying an organic phase by using anhydrous sodium sulfate, filtering, distilling off the solvent, separating and purifying a crude product by column chromatography, and drying by using petroleum ether and ethyl acetate as eluent to obtain a pure compound (molecular formula C) 17 H 14 OS)0.221g, purity more than 99% and reaction yield 83%.
1 H NMR(400MHz,DMSO-d 6 ):δ2.17(s,3H,CH),6.88(d,2H,ArH,J＝8.0Hz),6.98(d,2H,ArH,J＝8.0Hz),7.31-7.37(m,2H,ArH),7.47(t,1H,ArH,J＝8.0Hz),7.85(d,1H,ArH,J＝8.0Hz),7.93(d,1H,ArH,J＝8.0Hz),8.23(d,1H,ArH,J＝8.0Hz),10.24(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ158.8,136.3,134.7,134.6,132.4,130.5,130.3,129.1,129.0,128.6,128.0,126.6,124.6,123.7,119.0,108.7,20.9.
Example 5
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (1- (p-nitrophenylthio) -2-naphthol) comprises the following steps:
sequentially adding 0.6mmol (0.0864g) of 2-naphthol, 1.8mmol of p-nitrobenzophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, placing the flask in the air, heating at 80 ℃, stirring for reaction, monitoring the reaction by TLC (1 h), cooling to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate for dissolution, then adding 15ml of cold water for cooling, extracting twice with 20ml of ethyl acetate, drying an organic phase with anhydrous sodium sulfate, filtering, evaporating and removing the solvent, separating and purifying a crude product by column chromatography, and drying by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C) 16 H 11 NO 3 S)0.279g, purity more than 99% and reaction yield 83%.
1H NMR(400MHz,DMSO-d 6 ):δ7.12(d,2H,ArH,J＝8.8Hz),7.34-7.45(m,2H,ArH),7.52(t,1H,ArH,J＝7.5Hz),7.93(d,1H,ArH,J＝8.0Hz),8.06(d,3H,ArH,J＝8.8Hz),8.12(d,1H,ArH,J＝8.4Hz),10.67(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ159.2,148.7,144.8,135.9,133.5,129.2,129.1,128.5,125.8,124.5,124.0,123.9,119.0,105.6.
Example 6
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (1- (m-chlorophenylthio) -2-naphthol) comprises the following steps:
sequentially adding 0.6mmol (0.0864g) of 2-naphthol, 1.8mmol (0.259g) of m-chlorothiophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, heating and stirring the flask in the air at 80 ℃, monitoring the reaction by TLC (1 h for reaction), cooling the flask to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate for dissolution, adding 15ml of cold water for cooling, extracting the mixture twice by using 20ml of ethyl acetate, drying the organic phase by using anhydrous sodium sulfate, filtering and distilling the solvent, separating and purifying the crude product by column chromatography, and drying the crude product by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C) 16 H 11 ClOS)0.269g, purity greater than 99%, reaction yield 94%.
1 H NMR(400MHz,DMSO-d 6 ):δ6.94(d,2H,ArH,J＝12.0Hz),7.11(d,1H,ArH,J＝8.0Hz),7.20(t,1H,ArH,J＝8.0Hz),7.34-7.40(m,2H,ArH),7.50(t,1H,ArH,J＝8.0Hz),7.89(d,1H,ArH,J＝8.0Hz),8.00(d,1H,ArH,J＝12.0Hz),8.20(d,1H,ArH,J＝8.0Hz),10.47(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ159.1,140.9,136.2,134.1,133.1,131.0,129.1,128.3,125.2,125.1,124.7,124.2,123.9,119.0,107.0.
Example 7
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (1- (m-fluorophenylthio) -2-naphthol) comprises the following steps:
sequentially adding 0.6mmol (0.0864g) of 2-naphthol, 1.8mmol (0.230g) of m-fluorobenzothiophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, placing the flask in the air, heating at 80 ℃, stirring and reacting, monitoring the reaction by TLC (the reaction time is 1h), cooling to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate for dissolving, then adding 15ml of cold water for cooling, extracting twice by using 20ml of ethyl acetate, drying an organic phase by using anhydrous sodium sulfate, filtering and distilling off the solvent, and allowing a crude product to pass through a column Separating and purifying by chromatography, and drying with petroleum ether and ethyl acetate as eluent to obtain pure compound (molecular formula C) 16 H 11 FOS)0.259g, the purity is more than 99 percent, and the reaction yield is 96 percent.
1 H NMR(400MHz,DMSO-d 6 ):δ6.71-6.74(m,1H,ArH),6.82-6.84(m,1H,ArH),6.89-6.93(m,1H,ArH),7.22-7.28(m,1H,ArH),7.36-7.43(m,2H,ArH),7.50-7.55(m,1H,ArH),7.92(d,1H,ArH,J＝8.0Hz),8.03(d,1H,ArH,J＝9.2Hz),8.22(d,1H,ArH,J＝8.4Hz),10.52(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ164.1,161.7,159.1,141.2,141.1,136.2,133.1,131.2,131.1,129.1,128.3,124.3,123.8,122.0,121.9,119.0,112.6,112.3,112.2,111.9,107.0.
Example 8
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (1- (o-chlorophenylthio) -2-naphthol) comprises the following steps:
sequentially adding 0.6mmol (0.0864g) of 2-naphthol, 1.8mmol (0.259g) of o-chlorothiophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, heating and stirring the flask in the air at 80 ℃, monitoring the reaction by TLC (1 h for reaction), cooling the flask to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate for dissolution, adding 15ml of cold water for cooling, extracting the mixture twice by using 20ml of ethyl acetate, drying the organic phase by using anhydrous sodium sulfate, filtering and distilling the solvent, separating and purifying the crude product by column chromatography, and drying the crude product by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C) 16 H 11 ClOS)0.266g, purity greater than 99%, reaction yield 93%.
1 H NMR(400MHz,DMSO-d 6 ):δ6.31-6.33(m,1H,ArH),6.97-7.01(m,1H,ArH),7.03-7.07(m,1H,ArH),7.35(t,1H,ArH,J＝8.0Hz),7.41-7.50(m,3H,ArH),7.89(d,1H,ArH,J＝8.0Hz),8.01(d,1H,ArH,J＝8.0Hz),8.12(d,1H,ArH,J＝8.0Hz),10.55(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ159.4,137.3,136.2,133.2,130.1,129.9,129.2,129.1,128.3,127.9,126.2,126.1 124.1,123.9,119.1,106.1.
Example 9
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (1- (2, 4-difluorothiophenyl) -2-naphthol) comprises the following steps:
sequentially adding 0.6mmol (0.0864g) of 2-naphthol, 1.8mmol (0.263g) of 2, 4-difluorothiophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, heating and stirring the flask in the air at 80 ℃, monitoring the reaction by TLC (the reaction time is 2h), cooling the flask to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate for dissolving, then adding 15ml of cold water for cooling, extracting the solution twice by using 20ml of ethyl acetate, drying the organic phase by anhydrous sodium sulfate, filtering and distilling the solvent off, separating and purifying the crude product by column chromatography, and drying the crude product by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C) 16 H 10 F 2 OS)0.268g, purity greater than 99%, reaction yield 93%.
1 H NMR(400MHz,DMSO-d 6 ):δ6.56-6.62(m,1H,ArH),6.86-6.91(m,1H,ArH),7.30-7.41(m,3H,ArH),7.51-7.56(m,1H,ArH),7.90(d,1H,ArH,J＝8.0Hz),8.01(d,1H,ArH,J＝9.2Hz),8.25(d,1H,ArH,J＝8.4Hz),10.56(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ159.3,136.2,133.0,129.2,129.1,129.0,128.3,124.1,123.8,119.0,112.7,112.7,112.5,112.5,105.9,105.0,104.7,104.5.
Example 10
A synthetic method of a 1-thiophenyl-2-aromatic phenol compound (2- (4-chlorophenylthio) -1-hydroxypyrene) comprises the following steps:
0.6mmol (0.132g) of 1-hydroxypyrene, 1.8mmol (0.259g) of p-chlorothiophenol, and 0.6mmol (0.259g) of p-chlorothiophenol were sequentially added0672g) potassium tert-butoxide is added into a 10ml dry round-bottom flask, heated and stirred in air at 80 ℃ for reaction, monitored by TLC (reaction time is 4h, after the reaction is completed, cooled to 50 ℃, dissolved by adding 5ml ethyl acetate, cooled by adding 15ml cold water, extracted twice by using 20ml ethyl acetate, dried by anhydrous sodium sulfate for organic phase, filtered and evaporated to remove solvent, and the crude product is separated and purified by column chromatography, dried by using petroleum ether and ethyl acetate as eluent to obtain pure compound (molecular formula C) 22 H 13 ClOS)0.240g, purity greater than 98%, reaction yield 67%.
1 H NMR(400MHz,DMSO-d 6 ):δ7.21(d,2H,ArH,J＝8.8Hz),7.39(d,2H,ArH,J＝8.8Hz),7.95-8.06(m,3H,ArH),8.15-8.22(m,3H,ArH),8.26(s,1H,ArH),8.43(d,1H,ArH,J＝9.2Hz),10.41(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ152.0,135.9,131.8,131.6,131.4,131.1,130.4,130.0,129.7,127.4,127.3,127.2,126.1,125.5,125.3,125.2,124.8,122.1,120.0,117.9.
Example 11
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (1- (4-chlorophenylthio) -6-bromo-2-naphthol) comprises the following steps:
sequentially adding 0.6mmol (0.133g) of 6-bromo-2-naphthol, 1.8mmol (0.259g) of p-chlorothiophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, heating and stirring the flask in the air at 120 ℃, monitoring the reaction by TLC (the reaction time is 2h), cooling the flask to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate to dissolve the ethyl acetate, adding 15ml of cold water to cool the mixture, extracting the mixture twice with 20ml of ethyl acetate, drying the organic phase with anhydrous sodium sulfate, filtering and distilling off the solvent, separating and purifying the crude product by column chromatography, and drying the crude product by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C) 16 H 10 BrClOS)0.353g, purity more than 99% and reaction yield 97%.
1 H NMR(400MHz,DMSO-d 6 ):δ6.94(d,2H,ArH,J＝8.4Hz),7.26(d,2H,ArH,J＝8.4Hz),7.39(d,1H,ArH,J＝8.8Hz),7.62(dd,1H,ArH,J 1 ＝2.0Hz,J 2 ＝9.0Hz),7.98(d,1H,ArH,J＝8.8Hz),8.10(d,1H,ArH,J＝8.8Hz),8.17(d,1H,ArH,J＝2.0Hz),10.63(s,1H,OH). 13 C NMR(100MHz,DMSO-d6):δ164.1,141.7,139.7,136.8,135.8,135.5,135.1,134.7,134.6,134.3,134.1,132.6,131.5,125.0,121.5,112.7.
Example 12
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (1- (4-chlorophenylthio) -6-cyano-2-naphthol) comprises the following steps:
sequentially adding 0.6mmol (0.101g) of 6-cyano-2-naphthol, 1.8mmol (0.259g) of p-chlorothiophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, heating and stirring the flask in the air at 120 ℃, monitoring the reaction by TLC (the reaction time is 1h), cooling the flask to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate to dissolve the ethyl acetate, adding 15ml of cold water to cool the mixture, extracting the mixture twice by using 20ml of ethyl acetate, drying an organic phase by using anhydrous sodium sulfate, filtering and distilling off the solvent, separating and purifying a crude product by using column chromatography, and drying the crude product by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (a molecular formula C) 17 H 10 ClNOS)0.274g, purity more than 99%, reaction yield 88%.
1 H NMR(400MHz,DMSO-d 6 ):δ6.96(d,2H,ArH,J＝8.8Hz),7.27(d,2H,ArH,J＝8.4Hz),7.50(d,1H,ArH,J＝9.2Hz),7.78(dd,1H,ArH,J 1 ＝1.6Hz,J 2 ＝8.8Hz),8.13(d,1H,ArH,J＝9.2Hz),8.30(d,1H,ArH,J＝8.8Hz),8.54(d,1H,ArH,J＝1.4Hz),11.13(s,1H,OH). 13 C NMR(100MHz,DMSO-d6):δ161.2,137.7,136.1,134.8,133.1,129.7,129.0,128.3,127.6,127.4,125.2,120.3,119.2,107.9,105.5.
Example 13
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (1- (4-chlorophenylthio) -6-methyl-2-naphthol) comprises the following steps:
sequentially adding 0.6mmol (0.0648g) of p-cresol, 1.8mmol (0.259g) of p-chlorothiophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, heating and stirring the flask in the air at 80 ℃, monitoring the reaction by TLC (the reaction time is 2.5h), cooling the flask to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate for dissolving, then adding 15ml of cold water for cooling, extracting the solution twice by using 20ml of ethyl acetate, drying the organic phase by anhydrous sodium sulfate, filtering and distilling the solution, separating and purifying the crude product by column chromatography, and drying the crude product by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C) 13 H 11 ClOS)0.213g, purity more than 99% and reaction yield 85%.
1 H NMR(400MHz,DMSO-d 6 ):δ2.17(s,3H,CH),6.86(d,1H,ArH,J＝7.6Hz),7.06(d,2H,ArH,J＝7.6Hz),7.11(d,2H,ArH,J＝8.8Hz),7.35(d,2H,ArH,J＝8.4Hz),9.77(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ155.1,135.7,134.7,131.0,130.3,129.4,128.9,128.6,117.0,115.9,19.8.
Example 14
A method for synthesizing 1-thiophenyl-2-aromatic phenol compound (2- (4-chlorophenylthio) -3, 5-dimethylphenol) comprises the following steps:
adding 0.6mmol3, 5-dimethylphenol, 1.8mmol (0.259g) p-chlorothiophenol and 0.6mmol (0.0672g) potassium tert-butoxide into a 10ml dry round-bottom flask in sequence, placing the flask in the air, heating at 80 ℃, stirring and reacting, monitoring the reaction by TLC (reaction time is 2h), cooling to 50 ℃ after the reaction is completed, adding 5ml ethyl acetate for dissolving, adding 15ml cold water for cooling, extracting twice by using 20ml ethyl acetate, drying the organic phase by anhydrous sodium sulfate, filtering and distilling off the dissolved organic phaseSeparating and purifying the crude product by column chromatography, and drying with petroleum ether and ethyl acetate as eluent to obtain pure compound (formula C) 22 H 13 ClOS)0.208g, purity greater than 99%, reaction yield 93%.
1 H NMR(400MHz,DMSO-d 6 ):δ2.23(s,3H,CH),2.26(s,3H,CH),6.68(d,2H,ArH,J＝7.2Hz),6.91(d,2H,ArH,J＝8.4Hz),7.27(d,2H,ArH,J＝8.8Hz),9.70(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ159.5,144.0,141.3,137.7,129.5,129.2,127.3,122.9,114.9,112.5,21.4,21.3.
Example 15
A method for synthesizing 1-thiophenyl-2-aromatic phenolic compound (2- (4-chlorophenylthio) -3, 4-methyleneoxyphenol) comprises the following steps:
sequentially adding 0.6mmol (0.0816g) of 3, 4-methyleneoxyphenol, 1.8mmol (0.259g) of p-chlorothiophenol and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottom flask, heating and stirring the flask in the air at 80 ℃, monitoring the reaction by TLC (the reaction time is 0.5h), cooling the mixture to 50 ℃ after the reaction is completed, adding 5ml of ethyl acetate to dissolve the ethyl acetate, adding 15ml of cold water to cool the mixture, extracting the mixture twice by using 20ml of ethyl acetate, drying an organic phase by using anhydrous sodium sulfate, filtering and distilling the solvent, separating and purifying a crude product by using column chromatography, and drying the crude product by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (a molecular formula C) 14 H 11 ClO 2 S)0.245g, the purity is more than 99 percent, and the reaction yield is 88 percent.
1 H NMR(400MHz,DMSO-d 6 ):δ6.00(s,2H,CH),6.61(s,1H,ArH),6.90(s,1H,ArH),7.03(d,2H,ArH,J＝8.4Hz),7.31(d,2H,ArH,J＝8.8Hz),9.75(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ154.7,150.2,140.9,137.8,130.1,129.3,128.2,114.8,106.3,102.0,98.6.
Gram-order reactions are exemplified by the following example 1a
Sequentially adding 5mmol (0.72g) of 2-naphthol, 7.5mmol (1.08g) of p-chlorothiophenol and 2.5mmol (0.28g) of potassium tert-butoxide into a 25ml dry round-bottom flask, heating and stirring the flask in the air at 120 ℃, monitoring the reaction by TLC (thin layer chromatography) (the reaction time is 2h), cooling the flask to 50 ℃ after the reaction is completed, adding 10ml of ethyl acetate for dissolving, then adding 30ml of cold water for cooling, extracting the solution twice by using 25ml of ethyl acetate, drying the organic phase by anhydrous sodium sulfate, filtering and distilling the solution, separating and purifying the crude product by column chromatography, and drying the crude product by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C) 16 H 11 ClOS)1.40g, purity greater than 99%, reaction yield 97%.
1H NMR(400MHz,DMSO-d6):δ6.94(d,2H,ArH,J＝8.4Hz),7.25(d,2H,ArH,J＝8.4Hz),7.33-7.38(m,2H,ArH),7.50(t,1H,ArH,J＝7.8Hz),7.89(d,1H,ArH,J＝8Hz),7.98(d,1H,ArH,J＝8.8Hz),8.17(d,1H,ArH,J＝8.8Hz),10.39(s,1H,OH).13C NMR(100MHz,DMSO-d6):δ158.9,137.3,136.1,132.8,129.8,129.3,129.0,128.2,127.7,124.2,123.8,118.9,107.4
Gram-order reactions are exemplified by the following example 15a
Sequentially adding 5mmol (0.69g) of 3, 4-methyleneoxyphenol, 7.5mmol (1.08g) of p-chlorothiophenol and 2.5mmol (0.28g) of potassium tert-butoxide into a 10ml dry round-bottom flask, heating and stirring the flask in the air at 120 ℃, monitoring the reaction by TLC (the reaction time is 1h), cooling the flask to 50 ℃ after the reaction is completed, adding 10ml of ethyl acetate to dissolve the ethyl acetate, adding 30ml of cold water to cool the cooled flask, extracting the solution twice by using 25ml of ethyl acetate, drying an organic phase by using anhydrous sodium sulfate, filtering and distilling off the solvent, separating and purifying a crude product by using column chromatography, and drying the crude product by using petroleum ether and ethyl acetate as eluents to obtain a pure compound (a molecular formula C) 14 H 11 ClO 2 S)1.31g, purity more than 99%,the reaction yield was 93%.
1 H NMR(400MHz,DMSO-d 6 ):δ6.00(s,2H,CH),6.61(s,1H,ArH),6.90(s,1H,ArH),7.03(d,2H,ArH,J＝8.4Hz),7.31(d,2H,ArH,J＝8.8Hz),9.75(s,1H,OH). 13 C NMR(100MHz,DMSO-d 6 ):δ154.7,150.2,140.9,137.8,130.1,129.3,128.2,114.8,106.3,102.0,98.6.
Comparative ExampleScale and microreaction
The above examples show that the scale-up reactions of the present invention still give high yields, a significant advantage for this reaction.
The invention has been described in an illustrative manner, and it is to be understood that any simple variations, modifications or other equivalent changes which can be made by one skilled in the art without departing from the spirit of the invention fall within the scope of the invention.
Claims (6)
1. A method for synthesizing 1-thiophenyl-2-aromatic phenolic compounds is characterized by comprising the following steps:
in an air environment, stirring and reacting a first reactant, a thiophenol derivative and alkali at a heating temperature of 40-120 ℃, extracting, filtering, and carrying out column chromatography separation to obtain a 1-thiophenyl-2-aromatic phenol compound, wherein the ratio of the first reactant, the thiophenol derivative and the alkali is (1-3): (0.5-1.0), wherein the base is potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, potassium hydroxide, sodium hydroxide, potassium tert-butoxide, lithium tert-butoxide or diazabicyclo;
the first reactant is: 
Wherein R is 1 H, Br or CN;
the thiophenol derivative is
Wherein R is 2 Is Cl, Br, F, Me or NO 2 。
2. The method of claim 1, wherein the time for stirring the reaction is determined by thin layer chromatography.
3. The method of synthesis according to claim 2, wherein the stirring reaction time is at least 30 min.
4. The synthesis method of claim 3, wherein the eluent used for the column chromatographic separation is a mixture of ethyl acetate and petroleum ether, and the ratio of the ethyl acetate to the petroleum ether is 1 (30-50) in parts by volume.
5. The synthesis method according to claim 4, wherein the extraction is liquid separation extraction by adding ethyl acetate and water.
6. The synthesis process according to claim 5, characterized in that drying with anhydrous sodium sulfate is carried out before filtration.
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