CN112457173A - Simple synthesis method of meta-substituted phenol ether and phenol - Google Patents
Simple synthesis method of meta-substituted phenol ether and phenol Download PDFInfo
- Publication number
- CN112457173A CN112457173A CN202011405999.XA CN202011405999A CN112457173A CN 112457173 A CN112457173 A CN 112457173A CN 202011405999 A CN202011405999 A CN 202011405999A CN 112457173 A CN112457173 A CN 112457173A
- Authority
- CN
- China
- Prior art keywords
- meta
- substituted
- ether
- phenol
- synthetic method
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000008379 phenol ethers Chemical class 0.000 title claims abstract description 31
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical class OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 238000001308 synthesis method Methods 0.000 title abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 47
- 150000002989 phenols Chemical class 0.000 claims abstract description 23
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical class O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000002904 solvent Substances 0.000 claims abstract description 12
- 230000001590 oxidative effect Effects 0.000 claims abstract description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 239000007800 oxidant agent Substances 0.000 claims abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 51
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 48
- 238000003756 stirring Methods 0.000 claims description 40
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 31
- 239000011630 iodine Substances 0.000 claims description 31
- 229910052740 iodine Inorganic materials 0.000 claims description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 16
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 16
- 238000004440 column chromatography Methods 0.000 claims description 15
- 239000012074 organic phase Substances 0.000 claims description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 13
- 239000012153 distilled water Substances 0.000 claims description 13
- 239000010410 layer Substances 0.000 claims description 13
- LRMHFDNWKCSEQU-UHFFFAOYSA-N ethoxyethane;phenol Chemical compound CCOCC.OC1=CC=CC=C1 LRMHFDNWKCSEQU-UHFFFAOYSA-N 0.000 claims description 12
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 10
- CACORTWMILTTKB-UHFFFAOYSA-N 5-methyl-3-phenylcyclohex-2-en-1-one Chemical compound C1C(C)CC(=O)C=C1C1=CC=CC=C1 CACORTWMILTTKB-UHFFFAOYSA-N 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 229940071870 hydroiodic acid Drugs 0.000 claims description 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 5
- -1 Phenolic ethers Chemical class 0.000 claims description 5
- 239000012044 organic layer Substances 0.000 claims description 4
- SGZROIXVRAZISH-UHFFFAOYSA-N 5-[(4-methoxyphenyl)methyl]-3-phenylcyclohex-2-en-1-one Chemical compound COC1=CC=C(C=C1)CC2CC(=CC(=O)C2)C3=CC=CC=C3 SGZROIXVRAZISH-UHFFFAOYSA-N 0.000 claims description 3
- UMCTVQMMAUNCBN-UHFFFAOYSA-N 5-benzyl-3-phenylcyclohex-2-en-1-one Chemical compound C1C(CC(=O)C=C1C2=CC=CC=C2)CC3=CC=CC=C3 UMCTVQMMAUNCBN-UHFFFAOYSA-N 0.000 claims description 3
- SZWTWSYSPACLNQ-UHFFFAOYSA-N CC(C1)CC(C(C=C2)=CC=C2Br)=CC1=O Chemical compound CC(C1)CC(C(C=C2)=CC=C2Br)=CC1=O SZWTWSYSPACLNQ-UHFFFAOYSA-N 0.000 claims description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- XFLZRPBSGMDDBB-UHFFFAOYSA-N 5-[(4-methylphenyl)methyl]-3-phenylcyclohex-2-en-1-one Chemical compound CC1=CC=C(C=C1)CC2CC(=CC(=O)C2)C3=CC=CC=C3 XFLZRPBSGMDDBB-UHFFFAOYSA-N 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 claims 9
- 235000019441 ethanol Nutrition 0.000 claims 5
- 238000006467 substitution reaction Methods 0.000 claims 4
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 125000001033 ether group Chemical group 0.000 claims 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 239000012071 phase Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 11
- 239000000758 substrate Substances 0.000 abstract description 8
- 229910000510 noble metal Inorganic materials 0.000 abstract description 6
- 239000003054 catalyst Substances 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- 239000000126 substance Substances 0.000 description 30
- 238000005406 washing Methods 0.000 description 13
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 12
- 238000000605 extraction Methods 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000003921 oil Substances 0.000 description 7
- UGKJXUDEIHNMBJ-UHFFFAOYSA-N 1-methoxy-3-methyl-5-phenylbenzene Chemical compound COC1=CC(C)=CC(C=2C=CC=CC=2)=C1 UGKJXUDEIHNMBJ-UHFFFAOYSA-N 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- NPDIDUXTRAITDE-UHFFFAOYSA-N 1-methyl-3-phenylbenzene Chemical compound CC1=CC=CC(C=2C=CC=CC=2)=C1 NPDIDUXTRAITDE-UHFFFAOYSA-N 0.000 description 4
- 239000012501 chromatography medium Substances 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- BRDBTVDUEPOHFO-UHFFFAOYSA-N 3-methyl-5-phenylphenol Chemical compound CC1=CC(O)=CC(C=2C=CC=CC=2)=C1 BRDBTVDUEPOHFO-UHFFFAOYSA-N 0.000 description 2
- QPLGKBMWKLWTHG-UHFFFAOYSA-N 3-pentan-3-yloxypentane Chemical compound CCC(CC)OC(CC)CC QPLGKBMWKLWTHG-UHFFFAOYSA-N 0.000 description 2
- HHGCZJGAIUKCRF-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-3-phenylcyclohex-2-en-1-one Chemical compound C1C(CC(=O)C=C1C2=CC=CC=C2)CC3=CC=C(C=C3)Cl HHGCZJGAIUKCRF-UHFFFAOYSA-N 0.000 description 2
- PQUDSSMFRSFMEK-UHFFFAOYSA-N CC1=CC(C(C=C2)=CC=C2Br)=CC(OC)=C1 Chemical compound CC1=CC(C(C=C2)=CC=C2Br)=CC(OC)=C1 PQUDSSMFRSFMEK-UHFFFAOYSA-N 0.000 description 2
- LDVQFHPAHQKSOE-UHFFFAOYSA-N CC1=CC=C(CC2=CC(C3=CC=CC=C3)=CC(OC)=C2)C=C1 Chemical compound CC1=CC=C(CC2=CC(C3=CC=CC=C3)=CC(OC)=C2)C=C1 LDVQFHPAHQKSOE-UHFFFAOYSA-N 0.000 description 2
- FPSZYTMSLMMYAH-UHFFFAOYSA-N COC1=CC(CC(C=C2)=CC=C2Cl)=CC(C2=CC=CC=C2)=C1 Chemical compound COC1=CC(CC(C=C2)=CC=C2Cl)=CC(C2=CC=CC=C2)=C1 FPSZYTMSLMMYAH-UHFFFAOYSA-N 0.000 description 2
- INIOIBNBDCYHIL-UHFFFAOYSA-N COC1=CC=C(CC2=CC(C3=CC=CC=C3)=CC(OC)=C2)C=C1 Chemical compound COC1=CC=C(CC2=CC(C3=CC=CC=C3)=CC(OC)=C2)C=C1 INIOIBNBDCYHIL-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 238000006959 Williamson synthesis reaction Methods 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- ARURMXQZHORDBB-UHFFFAOYSA-N C(COCCC1=CC(CC2=CC=CC=C2)=CC(C2=CC=CC=C2)=C1)C1=CC(CC2=CC=CC=C2)=CC(C2=CC=CC=C2)=C1 Chemical compound C(COCCC1=CC(CC2=CC=CC=C2)=CC(C2=CC=CC=C2)=C1)C1=CC(CC2=CC=CC=C2)=CC(C2=CC=CC=C2)=C1 ARURMXQZHORDBB-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- JHIVVAPYMSGYDF-PTQBSOBMSA-N cyclohexanone Chemical class O=[13C]1CCCCC1 JHIVVAPYMSGYDF-PTQBSOBMSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000007336 electrophilic substitution reaction Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical compound [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/09—Preparation of ethers by dehydration of compounds containing hydroxy groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及生物医药技术领域，提供一种间位取代的酚醚的制备方法。以间位取代的环己烯酮的衍生物为反应原料，在醇溶剂及氧化剂条件下反应得到相应的间位取代的酚醚；反应过程易于控制、底物范围广，也为后续制备间位取代的酚提供更为简便的合成方法奠定基础；本发明还提供一种间位取代的酚的简便合成方法，以本发明制备的间位取代的酚醚为反应原料，用于解决现有技术制备间位取代的酚的过程中，需采用贵金属催化剂、反应控制难度大、底物范围窄的问题。The invention relates to the technical field of biomedicine and provides a preparation method of meta-substituted phenol ether. The derivative of meta-substituted cyclohexenone is used as the reaction raw material, and the corresponding meta-substituted phenolic ether is obtained by reacting under the conditions of alcohol solvent and oxidant; the reaction process is easy to control, the substrate range is wide, and it is also used for the subsequent preparation of meta-position. The substituted phenol provides a more convenient synthesis method and lays the foundation; the present invention also provides a simple and convenient synthesis method for the meta-substituted phenol, using the meta-substituted phenol ether prepared by the present invention as the reaction raw material, which is used to solve the problem of the prior art. In the process of preparing meta-substituted phenols, noble metal catalysts are required, the reaction control is difficult, and the substrate range is narrow.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to a simple synthesis method of meta-substituted phenol ether and phenol.
Background
Meta-substituted phenol ethers and phenols are widely used in the synthesis of high value-added chemicals, such as agrochemicals, polymers, pharmaceuticals, and the like. However, since both alkoxy groups and hydroxyl groups are strong ortho-para-positioning groups, it is difficult to directly introduce meta-substituents through electrophilic substitution reaction on the benzene ring of phenol ethers or phenols.
The current preparation of phenol ethers is mainly carried out by the Williamson synthesis, i.e. using sodium phenolate and a primary halogenated hydrocarbon under alkaline conditions. This method uses phenol as a starting material, but the Williamson synthesis does not solve the problem of introducing meta substituents, since meta phenol is necessary to prepare meta phenol ethers.
In the case of meta-substituted phenols, in recent years, researchers have used noble metal palladium-catalyzed oxidation of cyclohexanone derivatives for the preparation of meta-substituted phenols (y.izawa, d.pun and s.s.stahl, Science,2011,333,209), however, fine chemicals and pharmaceuticals have very strict requirements on the heavy metal content thereof, which puts high demands on how to remove the palladium catalyst in the product. It has also been reported that the meta-substituted phenol is prepared by the direct oxidation of cyclohexenone without metal catalysis (Green chem.,2016,18,6462), however, phenol is very easily oxidized, and this method may require very careful control of the reaction process due to the oxidation of the product phenol, and the substrate application range is narrow.
Aiming at the problems, the method for searching the meta-substituted phenol ether and the phenol synthesis method which do not need noble metal catalysts, are easy to control the reaction process and have wide substrate range has important significance.
Disclosure of Invention
The invention aims to overcome at least one defect (deficiency) of the prior art, provides a simple synthesis method of the meta-substituted phenol ether, is completely different from the preparation method of the meta-substituted phenol ether in the prior art, has the advantages of easy control of the reaction process and wide substrate range, and lays a foundation for providing a simpler synthesis method for the subsequent preparation of the meta-substituted phenol.
The invention also aims to provide a simple synthesis method of the meta-substituted phenol by using the phenol ether prepared by the method as a raw material, which is used for solving the problems of high reaction control difficulty and narrow substrate range due to the adoption of a noble metal catalyst in the process of preparing the meta-substituted phenol in the prior art.
The invention adopts the technical scheme that a simple synthesis method of meta-substituted phenol ether is characterized in that a meta-substituted cyclohexenone derivative is used as a reaction raw material, and the reaction is carried out under the conditions of an alcohol solvent and an oxidant to obtain the corresponding meta-substituted phenol ether. The mass ratio of the cyclohexenone derivative to the oxidant is 1: 1.5.
the reaction equation for the meta-substituted phenol ethers of the present invention is as follows:
further, the oxidant is iodine. The iodine simple substance is different from the noble metal catalyst commonly used in the prior art, the cost is low, and the iodine simple substance is easy to remove after the reaction is finished. Iodine simple substance belongs to one of halogens, is a crystal, and other halogen simple substances can also be used as the oxidant of the application, but other halogen simple substances are gas or liquid, so that the use process is inconvenient and the selectivity is poor.
Further, the meta-substituted phenol ether is prepared by the following method:
adding a meta-substituted cyclohexenone derivative, an alcohol solvent and an iodine simple substance into a thick-wall reaction bottle, stirring until the iodine simple substance is dissolved, screwing a reaction bottle cover to seal, and magnetically stirring for 5-7 hours at 70-90 ℃; stopping stirring, adding ethyl acetate, extracting with distilled water twice, washing with saturated sodium chloride solution once, and removing water layer; the organic phase is dried over anhydrous magnesium sulfate, filtered to remove the magnesium sulfate, the solvent is evaporated on a rotary evaporator, and the corresponding meta-substituted phenol ether is obtained by column chromatography purification.
Further, the structural formula of the derivative of the meta-substituted cyclohexenone is shown as
The structural formula of the meta-substituted phenol ether is shown in the specification
Wherein R is selected from one of alkyl and ether, R1One selected from alkyl, aryl or aryl derivatives; r2Selected from one of alkyl, aryl or aryl derivatives.
Further, the meta-substituted cyclohexenone derivative is one or more of 5-methyl-3-phenylcyclohex-2-enone, 5-methyl-3-p-bromophenyl cyclohex-2-enone, 5-benzyl-3-phenylcyclohex-2-enone, 5-p-tolylmethyl-3-phenylcyclohex-2-enone, 5-p-methoxybenzyl-3-phenylcyclohex-2-enone and 5-p-chlorobenzyl-3-phenylcyclohex-2-enone.
Furthermore, the alcoholic solution is one or more of methanol, ethanol, n-butanol, isopropanol, 3-pentanol and ethylene glycol monomethyl ether, and different kinds of phenol ethers can be obtained by using different alcohol solvents.
A simple synthesis method of meta-substituted phenol, which is characterized in that meta-substituted phenol ether obtained by any one of the simple synthesis methods is used as a raw material, and corresponding meta-substituted phenol is obtained under the action of hydroiodic acid; the amount of said substance of hydroiodic acid is at least 9 times the amount of the substance of the phenol ether.
Further, the meta-substituted phenol is prepared by the following method:
adding meta-substituted phenol ether and hydroiodic acid into a reaction bottle, refluxing for 2h under stirring, and cooling; adding water and ethyl acetate, separating an organic layer, washing twice with a saturated sodium bicarbonate solution, drying the organic phase with anhydrous magnesium sulfate, filtering to remove the magnesium sulfate, evaporating the solvent by a rotary evaporator, and purifying by column chromatography to obtain the corresponding meta-substituted phenol.
Phenol ethers can be viewed as a protective group for phenols, are effective in preventing phenols from being oxidized in an oxidizing environment, and are readily converted to phenols. The invention utilizes the stability of the phenol ether to generate the meta-substituted phenol ether in situ in the process of oxidizing the meta-substituted cyclohexenone derivative so as to avoid the defect of further oxidizing phenol in an oxidizing atmosphere. The resulting phenol ethers can be converted to the corresponding phenols in hydroiodic acid in high yields.
The reaction mechanism of the invention is shown as follows, taking the synthesis of 3-methyl-5-phenyl anisole as an example:
the reaction material 5-methyl-3-phenylcyclohex-2-enone firstly generates alpha-H iodination with elementary iodine under the heating condition to obtain A, A eliminates one molecule of hydrogen iodide to obtain B, and B can be interconverted into C. Finally, the C and methanol are catalyzed by the product hydrogen iodide to finally generate the 3-methyl-5-phenyl anisole.
Compared with the prior art, the invention has the beneficial effects that:
1) the invention provides a novel simple synthesis method for preparing meta-substituted phenol ether, which has the advantages of easily obtained raw materials, easily controlled reaction process and wide substrate application range, and can adjust the meta-substituent of the phenol ether through the substituent variety of cyclohexenone and adjust the alkoxy type of the phenol ether through the variety of alcohol;
2) the meta-substituted phenol ether prepared by the method is used for synthesizing the meta-substituted phenol, the operation is simple and convenient, a noble metal oxidant is not needed, the reaction is easy to control, and the substrate range is wide.
Detailed Description
The examples of the present invention are provided for illustrative purposes only and are not to be construed as limiting the invention.
Example 1
Preparation of 3-methyl-5-phenyl anisole
5-methyl-3-phenylcyclohex-2-enone (37mg, 0.2mmol) was added sequentially to a thick-walled reaction flask,methanol (2mL) and iodine (76mg, 0.3mmol) are stirred for 5 minutes at normal temperature, after the iodine is dissolved, the cover of the reaction bottle is screwed and sealed, and the reaction bottle is magnetically stirred for 6 hours at the temperature of 80 ℃. Stirring was stopped, 20mL of ethyl acetate was added, extraction was performed twice with distilled water, washing was performed once with a saturated sodium chloride solution, and the aqueous layer was separated. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove magnesium sulfate, evaporated on a rotary evaporator and purified by column chromatography (20: 1 by volume petroleum ether-ethyl acetate as the chromatography medium) to give 3-methyl-5-phenylanisole as a yellow oil (31mg, 78% yield).1H NMR(400MHz,CDCl3)δ7.57(dd,J＝8.2,1.1Hz,2H),7.41(t,J＝7.5Hz,2H),7.33(d,J＝7.4Hz,1H),7.00(s,1H),6.93(s,1H),6.72(s,1H),3.83(s,3H),2.39(s,3H)；13C NMR(101MHz,CDCl3)δ160.14,142.76,141.44,139.91,128.83,127.48,127.36,120.82,113.75,110.14,55.44,21.84。
Example 2
Preparation of 3-methyl-5-phenyl phenetole
Adding 5-methyl-3-phenylcyclohex-2-enone (37mg, 0.2mmol), ethanol (2mL) and iodine simple substance (76mg, 0.3mmol) into a thick-wall reaction bottle in sequence, stirring at normal temperature for 5 minutes, screwing a reaction bottle cover to seal after the iodine simple substance is dissolved, and magnetically stirring for 6 hours at the temperature of 80 ℃. Stirring was stopped, 20mL of ethyl acetate was added, extraction was performed twice with distilled water, washing was performed once with a saturated sodium chloride solution, and the aqueous layer was separated. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove magnesium sulfate, evaporated on a rotary evaporator and purified by column chromatography (20: 1 by volume petroleum ether-ethyl acetate as chromatography) to give 3-methyl-5-phenylphenyl ether as a yellow oil (36mg, 85% yield).1H NMR(400MHz,CDCl3)δ7.56(dt,J＝3.1,1.9Hz,2H),7.45–7.37(m,2H),7.36–7.29(m,1H),6.99(d,J＝0.4Hz,1H),6.93(s,1H),6.71(s,1H),4.07(q,J＝7.0Hz,2H),2.38(s,3H),1.43(t,J＝7.0Hz,3H)；13C NMR(101MHz,CDCl3)δ159.33,142.53,141.33,139.69,128.65,127.27,127.19,120.51,114.18,110.57,63.43,21.67,14.92。
Example 3
Preparation of 3-methyl-5-phenyl benzene n-butyl ether
Adding 5-methyl-3-phenylcyclohex-2-enone (37mg, 0.2mmol), n-butanol (2mL) and iodine simple substance (76mg, 0.3mmol) into a thick-wall reaction bottle in sequence, stirring at normal temperature for 5 minutes, screwing a reaction bottle cover to seal after the iodine simple substance is dissolved, and magnetically stirring at the temperature of 80 ℃ for 6 hours. Stirring was stopped, 20mL of ethyl acetate was added, extraction was performed twice with distilled water, washing was performed once with a saturated sodium chloride solution, and the aqueous layer was separated. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove magnesium sulfate, evaporated on a rotary evaporator and purified by column chromatography (20: 1 by volume petroleum ether-ethyl acetate as chromatography liquid) to give 3-methyl-5-phenylbenzene n-butyl ether as a pale yellow oil (43mg, 89% yield).1H NMR(400MHz,CDCl3)δ7.60–7.54(m,2H),7.44–7.37(m,2H),7.33(dt,J＝9.4,4.3Hz,1H),6.98(d,J＝0.6Hz,1H),6.93(t,J＝1.7Hz,1H),6.72(s,1H),4.00(t,J＝6.5Hz,2H),2.38(s,3H),1.78(dd,J＝8.4,6.7Hz,2H),1.56–1.45(m,3H),0.98(t,J＝7.4Hz,3H)；13C NMR(101MHz,CDCl3)δ159.73,142.70,141.53,139.84,128.81,127.43,127.37,120.61,114.38,110.75,67.88,31.61,21.84,19.47,14.05。
Example 4
Preparation of 3-methyl-5-phenyl isopropyl ether
Adding 5-methyl-3-phenylcyclohex-2-enone (37mg, 0.2mmol), isopropanol (2mL) and iodine simple substance (76mg, 0.3mmol) into a thick-wall reaction bottle in sequence, stirring for 5 minutes at normal temperature, screwing a reaction bottle cover to seal after the iodine simple substance is dissolved, and magnetically stirring for 6 hours at the temperature of 80 ℃. Stirring was stopped, 20mL of ethyl acetate was added, extraction was performed twice with distilled water, and washing was performed with a saturated sodium chloride solutionOnce washed, the aqueous layer was separated. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove magnesium sulfate, evaporated on a rotary evaporator, and purified by column chromatography (20: 1 by volume petroleum ether-ethyl acetate as chromatography liquid) to give 3-methyl-5-phenylpropyl isopropyl ether as a pale yellow oil (31mg, yield 68%).1H NMR(400MHz,CDCl3)δ7.56(dt,J＝3.0,1.8Hz,2H),7.45–7.38(m,2H),7.33(dt,J＝7.3,3.8,1.2Hz,1H),6.97(s,1H),6.92(d,J＝1.8Hz,1H),6.71(s,1H),4.60(dt,J＝12.1,6.1Hz,1H),2.38(s,3H),1.36(d,J＝6.1Hz,6H)；13C NMR(101MHz,CDCl3)δ158.26,142.56,141.36,139.70,128.64,127.24,127.18,120.47,115.58,111.93,69.86,22.17,21.67。
Example 5
Preparation of 3-methyl-5-phenylbenzene (3-pentyl) ether
Adding 5-methyl-3-phenylcyclohex-2-enone (37mg, 0.2mmol), 3-pentanol (2mL), iodine simple substance (76mg, 0.3mmol) into a thick-wall reaction flask in sequence, stirring for 5 minutes at normal temperature, screwing a reaction flask cover to seal after the iodine simple substance is dissolved, and magnetically stirring for 6 hours at the temperature of 80 ℃. Stirring was stopped, 20mL of ethyl acetate was added, extraction was performed twice with distilled water, washing was performed once with a saturated sodium chloride solution, and the aqueous layer was separated. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove magnesium sulfate, evaporated on a rotary evaporator and purified by column chromatography (20: 1 by volume petroleum ether-ethyl acetate as chromatography) to give 3-methyl-5-phenylbenzene (3-pentyl) ether as a pale yellow oil (40mg, 72% yield).1H NMR(400MHz,CDCl3)δ7.65–7.59(m,2H),7.50–7.43(m,2H),7.38(dt,J＝9.3,4.3Hz,1H),7.02(d,J＝0.5Hz,1H),6.99(d,J＝1.8Hz,1H),6.77(s,1H),4.22(t,J＝5.8Hz,1H),2.43(s,3H),1.80–1.70(m,4H),1.03(t,J＝7.4Hz,6H)；13C NMR(101MHz,CDCl3)δ159.14,142.54,141.40,139.67,128.64,127.22,127.19,120.37,115.67,112.03,80.15,26.15,21.68,9.64。
Example 6
Preparation of 3-methyl-5-phenyl methoxy ethyl ether
Adding 5-methyl-3-phenylcyclohex-2-enone (37mg, 0.2mmol), ethylene glycol monomethyl ether (2mL), iodine simple substance (76mg, 0.3mmol) into a thick-wall reaction bottle in sequence, stirring at normal temperature for 5 minutes, screwing a reaction bottle cover to seal after the iodine simple substance is dissolved, and magnetically stirring for 6 hours at the temperature of 80 ℃. Stirring was stopped, 20mL of ethyl acetate was added, extraction was performed twice with distilled water, washing was performed once with a saturated sodium chloride solution, and the aqueous layer was separated. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove magnesium sulfate, evaporated on a rotary evaporator and purified by column chromatography (20: 1 by volume petroleum ether-ethyl acetate as chromatography liquid) to give 3-methyl-5-phenyl methoxy ethyl ether as a yellow solid (25mg, 52% yield). m.p.45-46 ℃;1H NMR(400MHz,CDCl3)δ7.59–7.54(m,2H),7.44–7.38(m,2H),7.35–7.29(m,1H),7.00(s,1H),6.97(d,J＝1.9Hz,1H),6.75(s,1H),4.19–4.13(m,2H),3.78–3.73(m,2H),3.46(s,3H),2.38(s,3H)；13C NMR(101MHz,CDCl3)δ159.17,142.52,141.22,139.71,128.67,127.31,127.18,120.86,114.27,110.75,71.13,67.30,59.24,21.68。
example 7
Preparation of 3-methyl-5-p-bromophenyl anisole
Adding 5-methyl-3-p-bromophenyl cyclohex-2-enone (53mg, 0.2mmol), methanol (2mL) and iodine simple substance (76mg, 0.3mmol) into a thick-wall reaction bottle in sequence, stirring for 5 minutes at normal temperature, screwing a reaction bottle cover to seal after the iodine simple substance is dissolved, and magnetically stirring for 6 hours at the temperature of 80 ℃. Stirring was stopped, 20mL of ethyl acetate was added, extraction was performed twice with distilled water, washing was performed once with a saturated sodium chloride solution, and the aqueous layer was separated. Drying the organic phase over anhydrous magnesium sulfate, filtering to remove the magnesium sulfate, evaporating off the solvent on a rotary evaporator, and carrying out column chromatography (20: 1 by volume of petroleum ether-ethyl acetate)Ethyl acetate as chromatography) to give 3-methyl-5-p-bromophenyl anisole as a yellow oil (44mg, yield 80%).1H NMR(400MHz,CDCl3)δ7.57(d,J＝8.4Hz,2H),7.46(d,J＝8.4Hz,2H),6.98(s,1H),6.91(s,1H),6.76(s,1H),3.87(s,3H),2.42(s,3H)；13C NMR(101MHz,CDCl3)δ160.06,141.32,140.00,131.77,128.79,121.54,120.38,113.85,109.85,55.32,21.67。
Example 8
Preparation of 3-benzyl-5-phenylphenethyl ether
Adding 5-benzyl-3-phenylcyclohex-2-enone (52mg, 0.2mmol), ethanol (2mL) and iodine simple substance (76mg, 0.3mmol) into a thick-wall reaction bottle in sequence, stirring at normal temperature for 5 minutes, screwing a reaction bottle cover to seal after the iodine simple substance is dissolved, and magnetically stirring for 6 hours at the temperature of 80 ℃. Stirring was stopped, 20mL of ethyl acetate was added, extraction was performed twice with distilled water, washing was performed once with a saturated sodium chloride solution, and the aqueous layer was separated. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove magnesium sulfate, evaporated on a rotary evaporator and purified by column chromatography (20: 1 by volume petroleum ether-ethyl acetate as chromatography) to give 3-benzyl-5-phenylphenyl ether as a pale yellow oil (49mg, 85% yield).1H NMR(400MHz,CDCl3)δ7.59(d,J＝7.4Hz,2H),7.45(t,J＝7.5Hz,2H),7.40–7.20(m,7H),7.06(s,1H),7.00(s,1H),6.76(s,1H),4.09(q,J＝7.0Hz,2H),4.05(s,2H),1.45(t,J＝7.0Hz,3H)；13C NMR(101MHz,CDCl3)δ159.48,142.99,142.73,141.25,140.88,128.96,128.68,128.52,127.36,127.23,126.16,120.41,114.26,111.04,63.47,42.15,14.91。
Example 9
Preparation of 3-p-tolylmethyl-5-phenylanisole
Sequentially adding 5-p-toluene into a thick-wall reaction bottleMethyl-3-phenylcyclohex-2-enone (55mg, 0.2mmol), methanol (2mL), iodine simple substance (76mg, 0.3mmol), stirring at normal temperature for 5 minutes, screwing a reaction bottle cover to seal after the iodine simple substance is dissolved, and magnetically stirring at the temperature of 80 ℃ for 6 hours. Stirring was stopped, 20mL of ethyl acetate was added, extraction was performed twice with distilled water, washing was performed once with a saturated sodium chloride solution, and the aqueous layer was separated. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove magnesium sulfate, evaporated on a rotary evaporator and purified by column chromatography (20: 1 by volume petroleum ether-ethyl acetate as the chromatography medium) to give 3-p-tolylmethyl-5-phenylanisole as a colorless oil (41mg, 71% yield).1H NMR(400MHz,CDCl3)δ7.59(dd,J＝8.3,1.2Hz,2H),7.48–7.41(m,3H),7.14(d,J＝3.6Hz,4H),7.06(s,1H),6.99(d,J＝1.9Hz,1H),6.76(d,J＝1.6Hz,1H),4.00(s,2H),3.85(s,3H),2.35(s,3H)；13C NMR(101MHz,CDCl3)δ160.09,143.33,142.75,137.77,135.65,129.52,129.20,128.80,128.67,127.36,127.25,120.49,113.61,110.43,55.31,41.71,21.02。
Example 10
Preparation of 3-p-methoxybenzyl-5-phenyl anisole
Adding 5-p-methoxybenzyl-3-phenylcyclohex-2-enone (58mg, 0.2mmol), methanol (2mL) and iodine simple substance (76mg, 0.3mmol) into a thick-wall reaction flask in sequence, stirring for 5 minutes at normal temperature, screwing a reaction flask cover to seal after the iodine simple substance is dissolved, and magnetically stirring for 6 hours at the temperature of 80 ℃. Stirring was stopped, 20mL of ethyl acetate was added, extraction was performed twice with distilled water, washing was performed once with a saturated sodium chloride solution, and the aqueous layer was separated. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove magnesium sulfate, evaporated on a rotary evaporator and purified by column chromatography (20: 1 by volume petroleum ether-ethyl acetate as the chromatography medium) to give 3-p-methoxybenzyl-5-phenylanisole as a colorless oil (47mg, 78% yield).1H NMR(400MHz,CDCl3)δ7.58(dd,J＝5.2,3.2Hz,2H),7.47–7.41(m,2H),7.36(dt,J＝9.3,4.3Hz,1H),7.18(d,J＝8.7Hz,2H),7.04(s,1H),6.99(d,J＝2.0Hz,1H),6.87(d,J＝8.7Hz,2H),6.74(s,1H),3.98(s,2H),3.85(s,3H),3.81(s,3H)；13C NMR(101MHz,CDCl3)δ160.09,158.04,143.52,142.75,141.22,132.94,129.89,128.68,127.37,127.24,120.41,113.94,113.54,110.40,55.31,55.28,41.21。
Example 11
Preparation of 3-p-chlorobenzyl-5-phenyl anisole
Adding 5-p-chlorobenzyl-3-phenylcyclohex-2-enone (59mg, 0.2mmol), methanol (2mL) and iodine simple substance (76mg, 0.3mmol) into a thick-wall reaction bottle in sequence, stirring for 5 minutes at normal temperature, screwing a reaction bottle cover to seal after the iodine simple substance is dissolved, and magnetically stirring for 6 hours at the temperature of 80 ℃. Stirring was stopped, 20mL of ethyl acetate was added, extraction was performed twice with distilled water, washing was performed once with a saturated sodium chloride solution, and the aqueous layer was separated. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove magnesium sulfate, evaporated on a rotary evaporator and purified by column chromatography (20: 1 by volume petroleum ether-ethyl acetate as the chromatography medium) to give 3-p-chlorobenzyl-5-phenylanisole as a colorless oil (54mg, 87% yield).1H NMR(400MHz,CDCl3)δ7.58(d,J＝7.4Hz,2H),7.45(t,J＝7.5Hz,2H),7.37(t,J＝7.2Hz,1H),7.29(t,J＝4.0Hz,3H),7.19(d,J＝8.2Hz,2H),7.01(d,J＝6.6Hz,2H),6.72(s,1H),4.00(s,2H),3.86(s,3H)；13C NMR(101MHz,CDCl3)δ160.17,142.96,142.46,141.06,139.29,132.01,130.28,128.73,128.63,127.49,127.22,120.42,113.63,110.63,55.33,41.40。
Example 12
Preparation of 3-methyl-5-phenylphenol
3-methyl-5-phenylanisole (39mg, 0.2mmol) and 5ml hydroiodic acid (47 wt%) were added to a reaction flask, refluxed for 2 hours with stirring, and cooled. 20mL of water and 20mL of ethyl acetate were addedThe organic layer was separated, washed 2 times with saturated sodium bicarbonate solution, the organic phase was dried over anhydrous magnesium sulfate, filtered to remove magnesium sulfate, the solvent was evaporated on a rotary evaporator, and purified by column chromatography (petroleum ether-ethyl acetate in a volume ratio of 10: 1 as a chromatography) to give 3-methyl-5-phenylphenol (34mg, yield 93%) as a colorless liquid.1H NMR(400MHz,CDCl3)δ7.55-7.57(m,2H),7.41-7.44(m,2H),7.34-7.35(m,1H),7.00(s,1H),6.87(s,1H),6.65(s,1H),4.71(s,1H),2.3(s,3H)；13C NMR(101MHz,CDCl3)δ155.77,142.86,140.89,140.12,128.69,127.41,127.12,120.76,114.93,111.24,21.49。
The yield of the phenol ether prepared by the simple and convenient synthesis method of the meta-substituted phenol ether can reach 89%, and the yield of the meta-substituted phenol prepared by taking the meta-substituted phenol ether as a raw material can reach 93%.
It should be understood that the above-mentioned embodiments of the present invention are only examples for clearly illustrating the technical solutions of the present invention, and are not intended to limit the specific embodiments of the present invention. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention claims should be included in the protection scope of the present invention claims.
Claims (8)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011405999.XA CN112457173A (en) | 2020-12-02 | 2020-12-02 | Simple synthesis method of meta-substituted phenol ether and phenol |
| PCT/CN2020/135222 WO2022116242A1 (en) | 2020-12-02 | 2020-12-10 | Simple synthesis method for meta-substituted phenol ether and phenol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011405999.XA CN112457173A (en) | 2020-12-02 | 2020-12-02 | Simple synthesis method of meta-substituted phenol ether and phenol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112457173A true CN112457173A (en) | 2021-03-09 |
Family
ID=74804897
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011405999.XA Pending CN112457173A (en) | 2020-12-02 | 2020-12-02 | Simple synthesis method of meta-substituted phenol ether and phenol |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN112457173A (en) |
| WO (1) | WO2022116242A1 (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107721823B (en) * | 2016-08-10 | 2020-07-31 | 中国科学院大连化学物理研究所 | A kind of method for synthesizing m-cresol by dehydrogenation of 3-methylcyclohexenone |
-
2020
- 2020-12-02 CN CN202011405999.XA patent/CN112457173A/en active Pending
- 2020-12-10 WO PCT/CN2020/135222 patent/WO2022116242A1/en active Application Filing
Non-Patent Citations (5)
| Title |
|---|
| HORIUCHI, C. AKIRA: ""Iodine–Cerium(IV) Ammonium Nitrate"", 《E-EROS ENCYCLOPEDIA OF REAGENTS FOR ORGANIC SYNTHESISFJPEDIA OF REAGENTS FOR ORGANIC SYNTHESIS》 * |
| KORNFELD, EDMUND C.: ""A new synthesis of cinnoline derivatives: heterocyclic steroid analogs"", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
| TAMURA, YASUMITSU，ET AL.: ""An improved method for the conversion of cyclohexenones into anisoles"", 《CHEMISTRY & INDUSTRY》 * |
| YU FENG LIANG,ET AL.: ""Metal-Free I2-catalyzed highly selective dehydrogenative coupling of alcohols and cyclohexenones"", 《CHIN.J.CHEM.》 * |
| 刘鹰翔: "《药物合成反应 新世纪第2版》", August 2017 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2022116242A1 (en) | 2022-06-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | 1, n-rearrangement of allylic alcohols promoted by hot water: application to the synthesis of navenone B, a polyene natural product | |
| JP6990183B2 (en) | Chiral spirobindane skeleton compound and its production method | |
| JP5214609B2 (en) | Recovery of bis (diarylphenol) ligands during the production of isopulegol | |
| CN110483252B (en) | Method for synthesizing asymmetric triarylmethane derivative | |
| CN111718372B (en) | Axial chiral phosphine-ene ligand and preparation method and application thereof | |
| CN112142694A (en) | Polysubstituted tetrahydrofuran and tetrahydropyrane diene compound and preparation method thereof | |
| CN101323567B (en) | Process for preparing cinnamate and derivates thereof | |
| CN112457276B (en) | Method for synthesizing butylphthalide | |
| CN101186562B (en) | A rapid synthesis method of aromatic methyl ether with low energy consumption, high conversion rate and high selectivity | |
| CN112457173A (en) | Simple synthesis method of meta-substituted phenol ether and phenol | |
| CN109734571B (en) | Method for synthesizing alpha-F-beta-OH-carbonyl compound | |
| CN110563551B (en) | A method for synthesizing trans 2-en-4-yn-1-alcohol compounds | |
| CN109535120B (en) | Preparation method of 7-substituted-3, 4,4, 7-tetrahydrocyclobutane coumarin-5-ketone | |
| CN115073259B (en) | Preparation method for synthesizing 1, 4-diphenyl-1, 3-diacetylene or derivatives thereof | |
| JP3631070B2 (en) | Optically active fluorinated binaphthol derivatives | |
| CN102344431A (en) | Method for preparing nebivolol hydrochloride | |
| CN112679299B (en) | Preparation method of diarylmethane and derivatives thereof | |
| CN111423315A (en) | Method for synthesizing 2-arylacrolein diacetal by palladium-catalyzed Suzuki coupling reaction | |
| JP6918577B2 (en) | A method for producing an aromatic compound by a dehydrogenation reaction of a compound having a cycloalkane or cycloalkene structure using a heterogeneous palladium catalyst. | |
| CN109369357B (en) | A kind of method for preparing symmetrical diaryl ketone by catalytic oxidative carbonylation | |
| CN102924206B (en) | Water-phase green preparation method of 1,3-disubstituted-3-aryl allyl compound and application of 1,3-disubstituted-3-aryl allyl compound | |
| CN102617313A (en) | Sharing synthesis method for vanillin and isovanillin | |
| CN104710290A (en) | Green synthesis method of alpha, beta-unsaturated ketone compound | |
| CN108840788B (en) | Preparation method of resveratrol | |
| JP4825969B2 (en) | Method for producing tertiary alcohol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210309 |
|
| RJ01 | Rejection of invention patent application after publication |