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 abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 82
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical class SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000000376 reactant Substances 0.000 claims abstract description 8
- 238000010438 heat treatment Methods 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 177
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 48
- 238000010189 synthetic method Methods 0.000 claims description 27
- 239000003208 petroleum Substances 0.000 claims description 24
- 238000004809 thin layer chromatography Methods 0.000 claims description 23
- 238000004440 column chromatography Methods 0.000 claims description 21
- 239000003480 eluent Substances 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
- 150000001875 compounds Chemical class 0.000 claims description 18
- 238000001914 filtration Methods 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 8
- 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
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000000203 mixture Substances 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
- 238000000605 extraction Methods 0.000 claims description 3
- 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
- 238000000926 separation method Methods 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims 1
- 229910000024 caesium carbonate Inorganic materials 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 239000007800 oxidant agent Substances 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 230000001590 oxidative effect Effects 0.000 abstract description 2
- 238000006561 solvent free reaction Methods 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 28
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 20
- 230000035484 reaction time Effects 0.000 description 19
- 239000002904 solvent Substances 0.000 description 18
- 239000012043 crude product Substances 0.000 description 16
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
- 238000001035 drying Methods 0.000 description 11
- 229950011260 betanaphthol Drugs 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- -1 thiophenol free radical Chemical class 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- TUAMRELNJMMDMT-UHFFFAOYSA-N 3,5-xylenol Chemical compound CC1=CC(C)=CC(O)=C1 TUAMRELNJMMDMT-UHFFFAOYSA-N 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
- 230000008569 process Effects 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
- 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
- ZDEUGINAVLMAET-UHFFFAOYSA-N 3-fluorobenzenethiol Chemical compound FC1=CC=CC(S)=C1 ZDEUGINAVLMAET-UHFFFAOYSA-N 0.000 description 1
- OKIHXNKYYGUVTE-UHFFFAOYSA-N 4-Fluorothiophenol Chemical compound FC1=CC=C(S)C=C1 OKIHXNKYYGUVTE-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
- AXBVSRMHOPMXBA-UHFFFAOYSA-N 4-nitrothiophenol Chemical compound [O-][N+](=O)C1=CC=C(S)C=C1 AXBVSRMHOPMXBA-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
- CUMJYGKYSSVOFW-UHFFFAOYSA-N C1=CC(C)=CC=C1SC1=C(O)C=CC2=CC=CC=C12 Chemical compound C1=CC(C)=CC=C1SC1=C(O)C=CC2=CC=CC=C12 CUMJYGKYSSVOFW-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
- 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
- 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
- 230000008901 benefit Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- UHKPOGGUWJGGID-UHFFFAOYSA-N carbonic acid;cesium Chemical compound [Cs].OC(O)=O UHKPOGGUWJGGID-UHFFFAOYSA-N 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
- 238000013375 chromatographic separation Methods 0.000 description 1
- 239000000498 cooling water Substances 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 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
- 239000012071 phase Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 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
- 230000002194 synthesizing effect Effects 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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Description
技术领域technical field
本发明属于有机合成技术领域，具体来说涉及一种1-苯硫基-2-芳香酚类化合物的合成方法。The invention belongs to the technical field of organic synthesis, in particular to a method for synthesizing a 1-phenylthio-2-aromatic phenolic compound.
背景技术Background technique
硫元素广泛存在于商业药物、天然产物和一些基础材料中，使得碳硫键的构建在有机合成中非常重要。构建C-S键常用过渡金属催化芳基卤化物与硫醇或二硫化物发生交叉偶联反应来实现，这些合成方法往往需要用到昂贵的过渡金属催化剂、有机溶剂和化学当量的氧化剂。Sulfur is widely present in commercial drugs, natural products, and some basic materials, making the construction of carbon-sulfur bonds very important in organic synthesis. The construction of C-S bonds is usually achieved by the cross-coupling reaction of aryl halides with thiols or disulfides catalyzed by transition metals. These synthetic methods often require expensive transition metal catalysts, organic solvents and stoichiometric oxidants.
发明内容SUMMARY OF THE INVENTION
针对现有技术的不足，本发明的目的在于提供一种1-苯硫基-2-芳香酚类化合物的合成方法，该合成方法反应底物廉价易得，操作简便，反应时间短，生产成本低，污染少，后处理简单，反应产物单一，反应产率较高，尤其是氧化剂来源仅仅是空气，是一对环境友好、极其受大家欢迎的理想氧化来源。In view of the deficiencies of the prior art, the object of the present invention is to provide a synthetic method of a 1-phenylthio-2-aromatic phenolic compound, the synthetic method reaction substrate is cheap and easy to obtain, the operation is simple, the reaction time is short, and the production cost Low pollution, simple post-treatment, single reaction product and high reaction yield, especially the source of oxidant is only air, it is a pair of environmentally friendly and extremely popular ideal oxidation sources.
本发明的目的是通过下述技术方案予以实现的。The purpose of the present invention is achieved through the following technical solutions.
一种1-苯硫基-2-芳香酚类化合物的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound, comprising the following steps:
在空气环境下，将第一反应物、苯硫酚衍生物和碱在加热条件下搅拌反应，萃取，过滤，柱层析分离，得到1-苯硫基-2-芳香酚类化合物，其中，按物质的量份数计，所述第一反应物、苯硫酚衍生物和碱的比为1:(1～3)：(0.5～1.0)，所述碱为碳酸钾、碳酸钠、碳酸铯、磷酸钾、氢氧化钾、氢氧化钠、叔丁醇钾、叔丁醇锂或二氮杂二环(DBU)。In an air environment, the first reactant, the thiophenol derivative and the base are stirred and reacted under heating conditions, extracted, filtered, and separated by column chromatography to obtain 1-phenylthio-2-aromatic phenolic compounds, wherein, The ratio of the first reactant, the thiophenol derivative and the base is 1:(1-3):(0.5-1.0), and the base is potassium carbonate, sodium carbonate, carbonic acid Cesium, potassium phosphate, potassium hydroxide, sodium hydroxide, potassium tert-butoxide, lithium tert-butoxide or diazabicyclo (DBU).
在上述技术方案中，所述第一反应物为：
在上述技术方案中，所述苯硫酚衍生物为
在上述技术方案中，搅拌反应的温度为40～120℃。In the above technical solution, the temperature of the stirring reaction is 40-120°C.
在上述技术方案中，采用薄层色谱法确定搅拌反应的时间。In the above technical solution, the time of stirring reaction is determined by thin layer chromatography.
在上述技术方案中，所述搅拌反应的时间为至少30min，优选为30min～4h。In the above technical solution, the stirring reaction time is at least 30min, preferably 30min～4h.
在上述技术方案中，所述柱层析分离所使用的洗脱剂为乙酸乙酯和石油醚的混合物，按体积份数计，所述乙酸乙酯和石油醚的比为1:(30-50)。In technique scheme, the used eluent of described column chromatography is the mixture of ethyl acetate and petroleum ether, and in parts by volume, the ratio of described ethyl acetate and petroleum ether is 1:(30- 50).
在上述技术方案中，所述萃取为加入乙酸乙酯和水。In the above technical scheme, the extraction is adding ethyl acetate and water.
在上述技术方案中，在过滤前用无水硫酸钠进行干燥。In the above technical scheme, dry with anhydrous sodium sulfate before filtering.
本发明的合成方法为1-苯硫基-2-芳香酚类化合物提供了全新又简便高效的合成途径，具有良好的工业化前景和潜在应用价值，本发明的有益效果包括：The synthetic method of the present invention provides a new, simple and efficient synthetic route for 1-phenylthio-2-aromatic phenolic compounds, and has good industrialization prospects and potential application value. The beneficial effects of the present invention include:
1、高选择性合成单硫化产物。1. Highly selective synthesis of monosulfide products.
2、绿色无溶剂反应。2. Green solvent-free reaction.
3、反应能放大、效果依然非常好。3. The response can be amplified, and the effect is still very good.
具体实施方式Detailed ways
下面结合具体实施例进一步说明本发明的技术方案。The technical solutions of the present invention are further described below in conjunction with specific embodiments.
在本发明的具体实施方式中，合成所涉及的试剂以及药品为商业途径购买，均购买自天津试剂六厂，药品纯度均为分析纯，试剂和药品都是直接使用，没有经过任何前处理。In the specific embodiment of the present invention, the reagents and medicines involved in the synthesis were purchased through commercial channels, and were purchased from Tianjin Reagent No. 6 Factory. The purity of the medicines were all analytically pure, and the reagents and medicines were used directly without any pretreatment.
本发明的合成方法全程持续搅拌，搅拌所使用的电磁加热搅拌器的型号为NUOVAII(美国特马兰公司)；旋转蒸发仪的型号为RE-2000A(巩义市予华仪器责任有限公司)。核磁共振仪器型号：Bruker AV-400spectrometer，400MHz，DMSO-d6。The synthesis method of the present invention is continuously stirred throughout the whole process, and the model of the electromagnetic heating stirrer used in the stirring is NUOVAII (Temalan Company, USA); the model of the rotary evaporator is RE-2000A (Gongyi Yuhua Instrument Co., Ltd.). Nuclear magnetic resonance instrument model: Bruker AV-400spectrometer, 400MHz, DMSO-d6.
本发明中，在加热40～120℃条件下反应，通过薄层色谱法(TLC)检测反应进行的程度。在薄层色谱法中，使用尺寸为15mm×50mm的G254型硅胶板；展开剂为乙酸乙酯和石油醚的混合物，乙酸乙酯和石油醚的体积比为1:15In the present invention, the reaction is carried out under the condition of heating at 40 to 120° C., and the degree of progress of the reaction is detected by thin layer chromatography (TLC). In thin layer chromatography, a G254 silica gel plate with a size of 15mm × 50mm was used; the developing solvent was a mixture of ethyl acetate and petroleum ether, and the volume ratio of ethyl acetate and petroleum ether was 1:15
下述实施例柱层析分离所使用的洗脱剂为乙酸乙酯和石油醚的混合物，按体积份数计，乙酸乙酯和石油醚的比为1:30。The eluent used in the column chromatographic separation in the following examples is a mixture of ethyl acetate and petroleum ether, and the ratio of ethyl acetate and petroleum ether is 1:30 in parts by volume.
在检测过程中所使用ZF-I型三用紫外分析仪(上海驰唐)，所使用药品购买自天津试剂六厂，药品纯度都为分析纯，全部都是直接使用，没有经过任何前处理。通过TLC检测发现原料第一反应物消失，并且目标产物点不再变化时，标志本发明的合成方法反应结束，可以继续进行下一步的分离操作。The ZF-I type three-purpose UV analyzer (Shanghai Chitang) was used in the detection process. The drugs used were purchased from Tianjin Reagent No. 6 Factory. The purity of the drugs was analytically pure, and all of them were used directly without any pretreatment. When it is found by TLC detection that the first reactant of the raw material disappears and the target product point does not change any more, it marks the end of the reaction of the synthesis method of the present invention, and the next step of separation operation can be continued.
下述实施例中冷却水的温度为20℃。The temperature of the cooling water in the following examples was 20°C.
下述实施例均在空气中进行。The following examples are all carried out in air.
本发明合成方法的反应原理如下为：首先在碱性条件下，空气中的氧气将苯硫酚衍生物氧化生成过硫醚，进一步生成苯硫酚自由基，同时生成唯一的副产物水(a)；苯酚在苯硫酚自由基的作用下会生成三种自由基互变异构体(b)；苯硫酚自由基与较为稳定的苯酚自由基结合后，经过互变异构得到最终的产物(c)The reaction principle of the synthetic method of the present invention is as follows: at first under alkaline conditions, the oxygen in the air oxidizes the thiophenol derivative to generate persulfide, further generates thiophenol free radical, and simultaneously generates only by-product water (a ); phenol will generate three free radical tautomers (b) under the action of thiophenol free radical; after thiophenol free radical is combined with relatively stable phenol free radical, the final tautomer is obtained product (c)
实施例1Example 1
一种1-苯硫基-2-芳香酚类化合物(1-(对氯苯硫基)-2-萘酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (1-(p-chlorophenylthio)-2-naphthol), comprising the following steps:
依次将0.6mmol(0.0864g)2-萘酚、1.8mmol(0.259g)对氯苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为1.5h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂,产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C16H11ClOS)0.266g，纯度大于99％，反应收率93％。Add 0.6 mmol (0.0864 g) 2-naphthol, 1.8 mmol (0.259 g) p-chlorothiophenol, 0.6 mmol (0.0672 g) potassium tert-butoxide into a 10 ml dry round-bottomed flask in turn, and place it in the air at 80°C The reaction was heated and stirred, and the reaction was monitored by TLC (the reaction time was 1.5 h). After the reaction was completed, it was cooled to 50 ° C, and 5 ml of ethyl acetate was added to dissolve it, and then 15 ml of cold water was added for cooling. After the phase was dried over anhydrous sodium sulfate, the solvent was evaporated by filtration, the product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain 0.266 g of a pure compound (molecular formula C 16 H 11 ClOS), The purity is more than 99%, and the reaction yield is 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):δ158.9,137.3,136.1,132.8,129.8,129.3,129.0,128.2,127.7,124.2,123.8,118.9,107.41H 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
实施例2Example 2
一种1-苯硫基-2-芳香酚类化合物(1-(对溴苯硫基)-2-萘酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (1-(p-bromophenylthio)-2-naphthol), comprising the following steps:
依次将0.6mmol(0.0864g)2-萘酚、1.8mmol(0.334g)对溴苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为1h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂,粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C16H11BrOS)0.314g，纯度大于99％，反应收率95％。Add 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-bottomed flask in turn, and place it in the air at 80°C The reaction was heated and stirred, and the reaction was monitored by TLC (the reaction time was 1 h). After the reaction was completed, it was cooled to 50 ° C, and 5 ml of ethyl acetate was added to dissolve it, and then 15 ml of cold water was added to cool it. Then, the organic phase was extracted twice with 20 ml of ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was evaporated by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain 0.314 g of a pure compound (molecular formula C 16 H 11 BrOS), The purity is more than 99%, and the reaction yield is 95%.
1H NMR(400MHz,DMSO-d6):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).13C NMR(100MHz,DMSO-d6):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. 1 H NMR (400 MHz, DMSO-d 6 ): δ 6.90 (d, 2H, ArH, J=8.6 Hz), 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.
实施例3Example 3
一种1-苯硫基-2-芳香酚类化合物(1-(对氟苯硫基)-2-萘酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (1-(p-fluorophenylthio)-2-naphthol), comprising the following steps:
依次将0.6mmol(0.0864g)2-萘酚、1.8mmol(0.230g)对氟苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为1h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C16H11FOS)0.259g，纯度大于99％，反应收率96％。Add 0.6 mmol (0.0864 g) 2-naphthol, 1.8 mmol (0.230 g) p-fluorothiophenol, and 0.6 mmol (0.0672 g) potassium tert-butoxide in turn to a 10 ml dry round-bottomed flask, and place it in the air at 80°C The reaction was heated and stirred, and the reaction was monitored by TLC (the reaction time was 1 h). After the reaction was completed, it was cooled to 50° C., 5 ml of ethyl acetate was added to dissolve, and then 15 ml of cold water was added for cooling, and then extracted twice with 20 ml of ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was evaporated by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain 0.259 g of a pure compound (molecular formula C 16 H 11 FOS), The purity is more than 99%, and the reaction yield is 96%.
1H NMR(400MHz,DMSO-d6):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).13C NMR(100MHz,DMSO-d6):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. 1 H NMR (400MHz, DMSO-d 6 ): δ 7.00-7.08 (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). 13C 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.
实施例4Example 4
一种1-苯硫基-2-芳香酚类化合物(1-(对甲苯硫基)-2-萘酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (1-(p-tolylthio)-2-naphthol), comprising the following steps:
依次将0.6mmol(0.0864g)2-萘酚、1.8mmol(0.223g)对甲苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为1h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C17H14OS)0.221g，纯度大于99％，反应收率83％。Add 0.6mmol (0.0864g) of 2-naphthol, 1.8mmol (0.223g) of p-toluenethiophenol, and 0.6mmol (0.0672g) of potassium tert-butoxide into a 10ml dry round-bottomed flask in turn, and place it in the air to heat at 80°C The reaction was stirred and monitored by TLC (the reaction time was 1 h). After the reaction was complete, it was cooled to 50° C., and 5 ml of ethyl acetate was added to dissolve it, and then 15 ml of cold water was added to cool it. After drying over anhydrous sodium sulfate, the solvent was evaporated by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C 17 H 14 OS) 0.221 g with a purity of 0.221 g. More than 99%, the reaction yield is 83%.
1H NMR(400MHz,DMSO-d6):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).13CNMR(100MHz,DMSO-d6):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. 1 H NMR (400 MHz, DMSO-d 6 ): δ 2.17 (s, 3H, CH), 6.88 (d, 2H, ArH, J=8.0 Hz), 6.98 (d, 2H, ArH, J=8.0 Hz) ,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 CNMR (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.
实施例5Example 5
一种1-苯硫基-2-芳香酚类化合物(1-(对硝基苯硫基)-2-萘酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (1-(p-nitrophenylthio)-2-naphthol), comprising the following steps:
依次将0.6mmol(0.0864g)2-萘酚、1.8mmol对硝基苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为1h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C16H11NO3S)0.279g，纯度大于99％，反应收率83％。0.6mmol (0.0864g) of 2-naphthol, 1.8mmol of p-nitrothiophenol, 0.6mmol (0.0672g) of potassium tert-butoxide were successively added to a 10ml dry round-bottomed flask, and the reaction was heated and stirred at 80°C in the air. , TLC monitoring the reaction (reaction time is 1h), after the reaction is complete, cool to 50 ℃, add 5ml of ethyl acetate to dissolve, then add 15ml of cold water to cool, and then extract twice with 20ml of ethyl acetate, the organic phase is anhydrous After drying with sodium sulfate, the solvent was evaporated by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C 16 H 11 NO 3 S) 0.279 g with a purity of 0.279 g. More than 99%, the reaction yield is 83%.
1H NMR(400MHz,DMSO-d6):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).13C NMR(100MHz,DMSO-d6):δ159.2,148.7,144.8,135.9,133.5,129.2,129.1,128.5,125.8,124.5,124.0,123.9,119.0,105.6.1H NMR (400MHz, DMSO-d 6 ): δ 7.12 (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.
实施例6Example 6
一种1-苯硫基-2-芳香酚类化合物(1-(间氯苯硫基)-2-萘酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (1-(m-chlorophenylthio)-2-naphthol), comprising the following steps:
依次将0.6mmol(0.0864g)2-萘酚、1.8mmol(0.259g)间氯苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为1h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C16H11ClOS)0.269g，纯度大于99％，反应收率94％。Add 0.6 mmol (0.0864 g) 2-naphthol, 1.8 mmol (0.259 g) m-chlorothiophenol, and 0.6 mmol (0.0672 g) potassium tert-butoxide into a 10 ml dry round-bottomed flask in turn, and place it in the air at 80°C The reaction was heated and stirred, and the reaction was monitored by TLC (the reaction time was 1 h). After the reaction was completed, it was cooled to 50 ° C, and 5 ml of ethyl acetate was added to dissolve it, and then 15 ml of cold water was added to cool it. Then, the organic phase was extracted twice with 20 ml of ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was evaporated by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain 0.269 g of a pure compound (molecular formula C 16 H 11 ClOS), The purity is more than 99%, and the reaction yield is 94%.
1H NMR(400MHz,DMSO-d6):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).13C NMR(100MHz,DMSO-d6):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. 1 H NMR (400 MHz, DMSO-d 6 ): δ 6.94 (d, 2H, ArH, J=12.0 Hz), 7.11 (d, 1H, ArH, J=8.0 Hz), 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.
实施例7Example 7
一种1-苯硫基-2-芳香酚类化合物(1-(间氟苯硫基)-2-萘酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (1-(m-fluorophenylthio)-2-naphthol), comprising the following steps:
依次将0.6mmol(0.0864g)2-萘酚、1.8mmol(0.230g)间氟苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为1h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C16H11FOS)0.259g，纯度大于99％，反应收率96％。Add 0.6 mmol (0.0864 g) 2-naphthol, 1.8 mmol (0.230 g) m-fluorothiophenol, 0.6 mmol (0.0672 g) potassium tert-butoxide into a 10 ml dry round-bottomed flask in turn, and place it in the air at 80°C The reaction was heated and stirred, and the reaction was monitored by TLC (the reaction time was 1 h). After the reaction was completed, it was cooled to 50° C., 5 ml of ethyl acetate was added to dissolve, and then 15 ml of cold water was added for cooling, and then extracted twice with 20 ml of ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was evaporated by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain 0.259 g of a pure compound (molecular formula C 16 H 11 FOS), The purity is more than 99%, and the reaction yield is 96%.
1H NMR(400MHz,DMSO-d6):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).13C NMR(100MHz,DMSO-d6):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. 1 H NMR (400MHz, DMSO-d 6 ): δ 6.71-6.74 (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 (100 MHz, DMSO-d 6 ): δ 164.1, 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.
实施例8Example 8
一种1-苯硫基-2-芳香酚类化合物(1-(邻氯苯硫基)-2-萘酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (1-(o-chlorophenylthio)-2-naphthol), comprising the following steps:
依次将0.6mmol(0.0864g)2-萘酚、1.8mmol(0.259g)邻氯苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为1h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C16H11ClOS)0.266g，纯度大于99％，反应收率93％。Add 0.6 mmol (0.0864 g) 2-naphthol, 1.8 mmol (0.259 g) o-chlorothiophenol, 0.6 mmol (0.0672 g) potassium tert-butoxide in turn to a 10 ml dry round-bottomed flask, and place it in the air at 80°C The reaction was heated and stirred, and the reaction was monitored by TLC (the reaction time was 1 h). After the reaction was completed, it was cooled to 50° C., 5 ml of ethyl acetate was added to dissolve, and then 15 ml of cold water was added for cooling, and then extracted twice with 20 ml of ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was evaporated by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain 0.266 g of a pure compound (molecular formula C 16 H 11 ClOS), The purity is more than 99%, and the reaction yield is 93%.
1H NMR(400MHz,DMSO-d6):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).13C NMR(100MHz,DMSO-d6):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. 1 H NMR (400MHz, DMSO-d 6 ): δ 6.31-6.33 (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 (100 MHz, DMSO-d 6 ): δ 159.4, 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.
实施例9Example 9
一种1-苯硫基-2-芳香酚类化合物(1-(2,4-二氟苯硫基)-2-萘酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (1-(2,4-difluorophenylthio)-2-naphthol), comprising the following steps:
依次将0.6mmol(0.0864g)2-萘酚、1.8mmol(0.263g)2,4-二氟苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为2h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C16H10F2OS)0.268g，纯度大于99％，反应收率93％。0.6mmol (0.0864g) of 2-naphthol, 1.8mmol (0.263g) of 2,4-difluorothiophenol, 0.6mmol (0.0672g) of potassium tert-butoxide were added to a 10ml dry round-bottomed flask in turn, and placed in a The reaction was heated and stirred at 80 °C in the air, and the reaction was monitored by TLC (the reaction time was 2 h). After the reaction was completed, it was cooled to 50 °C, dissolved in 5 ml of ethyl acetate, and then cooled by adding 15 ml of cold water, and then extracted with 20 ml of ethyl acetate. Second, after the organic phase was dried over anhydrous sodium sulfate, the solvent was evaporated by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C 16 H 10 F ). 2 OS) 0.268g, the purity is more than 99%, and the reaction yield is 93%.
1H NMR(400MHz,DMSO-d6):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).13C NMR(100MHz,DMSO-d6):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. 1 H NMR (400MHz, DMSO-d 6 ): δ 6.56-6.62 (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.
实施例10Example 10
一种1-苯硫基-2-芳香酚类化合物(2-(4-氯苯硫基)-1-羟基芘)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (2-(4-chlorophenylthio)-1-hydroxypyrene), comprising the following steps:
依次将0.6mmol(0.132g)1-羟基芘、1.8mmol(0.259g)对氯苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为4h，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C22H13ClOS)0.240g，纯度大于98％，反应收率67％。Add 0.6mmol (0.132g) 1-hydroxypyrene, 1.8mmol (0.259g) p-chlorothiophenol, 0.6mmol (0.0672g) potassium tert-butoxide into a 10ml dry round-bottomed flask in turn, and place it in the air at 80°C The reaction was heated and stirred, and the reaction was monitored by TLC (the reaction time was 4 h. After the reaction was complete, it was cooled to 50° C., 5 ml of ethyl acetate was added to dissolve, and then 15 ml of cold water was added for cooling, and then extracted twice with 20 ml of ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was evaporated by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C 22 H 13 ClOS) 0.240 g with a purity of 0.240 g. More than 98%, the reaction yield is 67%.
1H NMR(400MHz,DMSO-d6):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).13C NMR(100MHz,DMSO-d6):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. 1 H NMR (400 MHz, DMSO-d 6 ): δ 7.21 (d, 2H, ArH, J=8.8 Hz), 7.39 (d, 2H, ArH, J=8.8 Hz), 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, 122.9.1, 12
实施例11Example 11
一种1-苯硫基-2-芳香酚类化合物(1-(4-氯苯硫基)-6-溴-2-萘酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (1-(4-chlorophenylthio)-6-bromo-2-naphthol), comprising the following steps:
依次将0.6mmol(0.133g)6-溴-2-萘酚、1.8mmol(0.259g)对氯苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中120℃加热搅拌反应，TLC监测反应(反应时间为2h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C16H10BrClOS)0.353g，纯度大于99％，反应收率97％。Add 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-bottomed flask in turn, and place it in a The reaction was heated and stirred at 120 °C in the air, and the reaction was monitored by TLC (the reaction time was 2 h). After the reaction was complete, it was cooled to 50 °C, dissolved in 5 ml of ethyl acetate, and then cooled by adding 15 ml of cold water, and then extracted with 20 ml of ethyl acetate. Second, after the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C 16 H 10 BrClOS ). ) 0.353g, the purity is more than 99%, and the reaction yield is 97%.
1H NMR(400MHz,DMSO-d6):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,J1＝2.0Hz,J2＝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).13C 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. 1 H NMR (400 MHz, DMSO-d 6 ): δ 6.94 (d, 2H, ArH, J=8.4 Hz), 7.26 (d, 2H, ArH, J=8.4 Hz), 7.39 (d, 1H, ArH, J=8.8Hz), 7.62 (dd, 1H, ArH, J1 = 2.0Hz, J2=9.0Hz ) , 7.98 (d, 1H, ArH, J=8.8Hz), 8.10 (d, 1H, ArH, J = 8.8 Hz), 8.17 (d, 1H, ArH, J = 2.0 Hz), 10.63 (s, 1H, OH). 13 C NMR (100 MHz, DMSO-d6): δ 164.1, 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.
实施例12Example 12
一种1-苯硫基-2-芳香酚类化合物(1-(4-氯苯硫基)-6-氰基-2-萘酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (1-(4-chlorophenylthio)-6-cyano-2-naphthol), comprising the following steps:
依次将0.6mmol(0.101g)6-氰基-2-萘酚、1.8mmol(0.259g)对氯苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中120℃加热搅拌反应，TLC监测反应(反应时间为1h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C17H10ClNOS)0.274g，纯度大于99％，反应收率88％。Add 0.6 mmol (0.101 g) 6-cyano-2-naphthol, 1.8 mmol (0.259 g) p-chlorothiophenol, 0.6 mmol (0.0672 g) potassium tert-butoxide into a 10 ml dry round-bottomed flask in turn, set The reaction was heated and stirred at 120 °C in the air, and the reaction was monitored by TLC (reaction time was 1 h). After the reaction was completed, it was cooled to 50 °C, and 5 ml of ethyl acetate was added to dissolve it. Then 15 ml of cold water was added for cooling, and then extracted with 20 ml of ethyl acetate. Twice, after the organic phase was dried over anhydrous sodium sulfate, the solvent was evaporated by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C 17 H 10 ). ClNOS) 0.274g, the purity is more than 99%, and the reaction yield is 88%.
1H NMR(400MHz,DMSO-d6):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,J1＝1.6Hz,J2＝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).13C 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. 1 H NMR (400 MHz, DMSO-d 6 ): δ 6.96 (d, 2H, ArH, J=8.8 Hz), 7.27 (d, 2H, ArH, J=8.4 Hz), 7.50 (d, 1H, ArH, J=9.2Hz), 7.78(dd,1H,ArH,J1 = 1.6Hz,J2=8.8Hz ) ,8.13(d,1H,ArH,J=9.2Hz),8.30(d,1H,ArH,J = 8.8 Hz), 8.54 (d, 1H, ArH, J = 1.4 Hz), 11.13 (s, 1H, OH). 13 C NMR (100 MHz, DMSO-d6): δ 161.2, 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.
实施例13Example 13
一种1-苯硫基-2-芳香酚类化合物(1-(4-氯苯硫基)-6-甲基-2-萘酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (1-(4-chlorophenylthio)-6-methyl-2-naphthol), comprising the following steps:
依次将0.6mmol(0.0648g)对甲苯酚、1.8mmol(0.259g)对氯苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为2.5h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C13H11ClOS)0.213g，纯度大于99％，反应收率85％。Add 0.6 mmol (0.0648 g) p-cresol, 1.8 mmol (0.259 g) p-chlorothiophenol, 0.6 mmol (0.0672 g) potassium tert-butoxide into a 10 ml dry round-bottomed flask in turn, and heat at 80 °C in the air Stir the reaction, monitor the reaction by TLC (the reaction time is 2.5h), after the reaction is complete, cool to 50 ° C, add 5 ml of ethyl acetate to dissolve, then add 15 ml of cold water to cool, and then extract twice with 20 ml of ethyl acetate, the organic phase After drying over anhydrous sodium sulfate, the solvent was evaporated by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain 0.213 g of a pure compound (molecular formula C 13 H 11 ClOS), The purity is more than 99%, and the reaction yield is 85%.
1H NMR(400MHz,DMSO-d6):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).13C NMR(100MHz,DMSO-d6):δ155.1,135.7,134.7,131.0,130.3,129.4,128.9,128.6,117.0,115.9,19.8. 1 H NMR (400 MHz, DMSO-d 6 ): δ 2.17 (s, 3H, CH), 6.86 (d, 1H, ArH, J=7.6 Hz), 7.06 (d, 2H, ArH, J=7.6 Hz) , 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.
实施例14Example 14
一种1-苯硫基-2-芳香酚类化合物(2-(4-氯苯硫基)-3,5-二甲基苯酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (2-(4-chlorophenylthio)-3,5-dimethylphenol), comprising the following steps:
依次将0.6mmol3,5-二甲基苯酚、1.8mmol(0.259g)对氯苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为2h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C22H13ClOS)0.208g，纯度大于99％，反应收率93％。0.6 mmol 3,5-dimethylphenol, 1.8 mmol (0.259 g) p-chlorothiophenol, 0.6 mmol (0.0672 g) potassium tert-butoxide were successively added to a 10 ml dry round-bottomed flask, and heated at 80 °C in the air Stir the reaction, monitor the reaction by TLC (reaction time is 2h), after the reaction is complete, cool to 50°C, add 5ml of ethyl acetate to dissolve, then add 15ml of cold water to cool, and then extract twice with 20ml of ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was evaporated by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C 22 H 13 ClOS) 0.208 g with a purity of 0.208 g. More than 99%, the reaction yield is 93%.
1H NMR(400MHz,DMSO-d6):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).13C NMR(100MHz,DMSO-d6):δ159.5,144.0,141.3,137.7,129.5,129.2,127.3,122.9,114.9,112.5,21.4,21.3. 1 H NMR (400MHz, DMSO-d 6 ): δ 2.23 (s, 3H, CH), 2.26 (s, 3H, CH), 6.68 (d, 2H, ArH, J=7.2 Hz), 6.91 (d, 2H, ArH, J=8.4Hz), 7.27 (d, 2H, ArH, J=8.8Hz), 9.70 (s, 1H, OH). 13 C NMR (100 MHz, DMSO-d 6 ): δ 159.5, 144.0, 141.3 ,137.7,129.5,129.2,127.3,122.9,114.9,112.5,21.4,21.3.
实施例15Example 15
一种1-苯硫基-2-芳香酚类化合物(2-(4-氯苯硫基)-3,4-亚甲氧基苯酚)的合成方法，包括以下步骤：A synthetic method of 1-phenylthio-2-aromatic phenolic compound (2-(4-chlorophenylthio)-3,4-methyleneoxyphenol), comprising the following steps:
依次将0.6mmol(0.0816g)3,4-亚甲氧基苯酚、1.8mmol(0.259g)对氯苯硫酚、0.6mmol(0.0672g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中80℃加热搅拌反应，TLC监测反应(反应时间为0.5h)，待反应完全后，冷却至50℃，加入5ml乙酸乙酯溶解，然后加入15ml冷水冷却后，再用乙酸乙酯20ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C14H11ClO2S)0.245g，纯度大于99％，反应收率88％。0.6mmol (0.0816g) of 3,4-methyleneoxyphenol, 1.8mmol (0.259g) of p-chlorothiophenol, and 0.6mmol (0.0672g) of potassium tert-butoxide were successively added to a 10ml dry round-bottomed flask, and set The reaction was heated and stirred at 80°C in the air, and the reaction was monitored by TLC (the reaction time was 0.5h). After the reaction was completed, it was cooled to 50°C, and 5ml of ethyl acetate was added to dissolve it. Then 15ml of cold water was added to cool it, and then 20ml of ethyl acetate was added. Extracted twice, the organic phase was dried over anhydrous sodium sulfate, filtered and evaporated to remove the solvent, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C 14 H ) 11 ClO 2 S) 0.245g, the purity is more than 99%, and the reaction yield is 88%.
1H NMR(400MHz,DMSO-d6):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).13C NMR(100MHz,DMSO-d6):δ154.7,150.2,140.9,137.8,130.1,129.3,128.2,114.8,106.3,102.0,98.6. 1 H NMR (400MHz, DMSO-d 6 ): δ 6.00(s, 2H, CH), 6.61(s, 1H, ArH), 6.90(s, 1H, ArH), 7.03(d, 2H, ArH, J = 8.4 Hz), 7.31 (d, 2H, ArH, J = 8.8 Hz), 9.75 (s, 1H, OH). 13 C NMR (100 MHz, DMSO-d 6 ): δ 154.7, 150.2, 140.9, 137.8, 130.1, 129.3, 128.2, 114.8, 106.3, 102.0, 98.6.
克级反应以如下实施例1a为例The gram-level reaction takes the following example 1a as an example
依次将5mmol(0.72g)2-萘酚、7.5mmol(1.08g)对氯苯硫酚、2.5mmol(0.28g)叔丁醇钾加入25ml干燥的圆底烧瓶内，置于空气中120℃加热搅拌反应，TLC监测反应(反应时间为2h)，待反应完全后，冷却至50℃，加入10ml乙酸乙酯溶解，然后加入30ml冷水冷却后，再用乙酸乙酯25ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C16H11ClOS)1.40g，纯度大于99％，反应收率97％。Add 5mmol (0.72g) 2-naphthol, 7.5mmol (1.08g) p-chlorothiophenol, 2.5mmol (0.28g) potassium tert-butoxide into a 25ml dry round-bottomed flask in turn, and heat at 120°C in the air The reaction was stirred and monitored by TLC (the reaction time was 2h). After the reaction was complete, it was cooled to 50° C., dissolved in 10 ml of ethyl acetate, and then cooled by adding 30 ml of cold water. The organic phase was extracted twice with 25 ml of ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was evaporated by filtration, and the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain 1.40 g of a pure compound (molecular formula C 16 H 11 ClOS) with a purity of 1.40 g. More than 99%, the reaction yield is 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):δ158.9,137.3,136.1,132.8,129.8,129.3,129.0,128.2,127.7,124.2,123.8,118.9,107.41H 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
克级反应以如下实施例15a为例The gram-level reaction takes the following example 15a as an example
依次将5mmol(0.69g)3,4-亚甲氧基苯酚、7.5mmol(1.08g)对氯苯硫酚、2.5mmol(0.28g)叔丁醇钾加入10ml干燥的圆底烧瓶内，置于空气中120℃加热搅拌反应，TLC监测反应(反应时间为1h)，待反应完全后，冷却至50℃，加入10ml乙酸乙酯溶解，然后加入30ml冷水冷却后，再用乙酸乙酯25ml萃取两次，有机相经无水硫酸钠干燥后，过滤蒸除溶剂，粗产品经柱层析分离提纯，采用石油醚和乙酸乙酯作为洗脱剂干燥即得到纯的化合物(分子式C14H11ClO2S)1.31g，纯度大于99％，反应收率93％。5mmol (0.69g) of 3,4-methyleneoxyphenol, 7.5mmol (1.08g) of p-chlorothiophenol, 2.5mmol (0.28g) of potassium tert-butoxide were successively added to a 10ml dry round-bottomed flask, and placed in a The reaction was heated and stirred at 120 °C in the air, and the reaction was monitored by TLC (the reaction time was 1 h). After the reaction was completed, it was cooled to 50 °C, dissolved in 10 ml of ethyl acetate, and then cooled by adding 30 ml of cold water, and then extracted with 25 ml of ethyl acetate. Second, after the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by filtration, the crude product was separated and purified by column chromatography, and dried using petroleum ether and ethyl acetate as eluents to obtain a pure compound (molecular formula C 14 H 11 ClO 2 S) 1.31 g, the purity is more than 99%, and the reaction yield is 93%.
1H NMR(400MHz,DMSO-d6):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).13C NMR(100MHz,DMSO-d6):δ154.7,150.2,140.9,137.8,130.1,129.3,128.2,114.8,106.3,102.0,98.6. 1 H NMR (400MHz, DMSO-d 6 ): δ 6.00(s, 2H, CH), 6.61(s, 1H, ArH), 6.90(s, 1H, ArH), 7.03(d, 2H, ArH, J = 8.4 Hz), 7.31 (d, 2H, ArH, J = 8.8 Hz), 9.75 (s, 1H, OH). 13 C NMR (100 MHz, DMSO-d 6 ): δ 154.7, 150.2, 140.9, 137.8, 130.1, 129.3, 128.2, 114.8, 106.3, 102.0, 98.6.
表 克级和微量反应比较Table Gram-level and micro-reaction comparison
上述实施例可表明，本发明放大反应，依然能够得到高产率，为此反应一显著优点。The above examples can show that the scaled-up reaction of the present invention can still obtain high yield, which is a significant advantage of the reaction.
以上对本发明做了示例性的描述，应该说明的是，在不脱离本发明的核心的情况下，任何简单的变形、修改或者其他本领域技术人员能够不花费创造性劳动的等同替换均落入本发明的保护范围。The present invention has been exemplarily described above. It should be noted that, without departing from the core of the present invention, any simple deformation, modification or other equivalent replacements that can be performed by those skilled in the art without creative effort fall into the scope of the present invention. the scope of protection of the invention.
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