CN112645821A - Method for synthesizing aryl benzyl ether compound - Google Patents
Method for synthesizing aryl benzyl ether compound Download PDFInfo
- Publication number
- CN112645821A CN112645821A CN202110090038.2A CN202110090038A CN112645821A CN 112645821 A CN112645821 A CN 112645821A CN 202110090038 A CN202110090038 A CN 202110090038A CN 112645821 A CN112645821 A CN 112645821A
- Authority
- CN
- China
- Prior art keywords
- synthesizing
- ether compounds
- benzyl ether
- reaction
- aryl benzyl
- 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
- -1 aryl benzyl ether compound Chemical class 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 22
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 19
- 239000003054 catalyst Substances 0.000 claims abstract description 36
- 150000002989 phenols Chemical class 0.000 claims abstract description 22
- 239000007800 oxidant agent Substances 0.000 claims abstract description 11
- 230000001590 oxidative effect Effects 0.000 claims abstract description 11
- 239000000047 product Substances 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 37
- 238000004440 column chromatography Methods 0.000 claims description 18
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 claims description 14
- HBMCQTHGYMTCOF-UHFFFAOYSA-N 4-hydroxyphenyl acetate Chemical compound CC(=O)OC1=CC=C(O)C=C1 HBMCQTHGYMTCOF-UHFFFAOYSA-N 0.000 claims description 8
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 claims description 8
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical class C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- HOLHYSJJBXSLMV-UHFFFAOYSA-N 2,6-dichlorophenol Chemical compound OC1=C(Cl)C=CC=C1Cl HOLHYSJJBXSLMV-UHFFFAOYSA-N 0.000 claims description 4
- JECYUBVRTQDVAT-UHFFFAOYSA-N 2-acetylphenol Chemical compound CC(=O)C1=CC=CC=C1O JECYUBVRTQDVAT-UHFFFAOYSA-N 0.000 claims description 4
- BAYGVMXZJBFEMB-UHFFFAOYSA-N 4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1 BAYGVMXZJBFEMB-UHFFFAOYSA-N 0.000 claims description 4
- QHPQWRBYOIRBIT-UHFFFAOYSA-N 4-tert-butylphenol Chemical compound CC(C)(C)C1=CC=C(O)C=C1 QHPQWRBYOIRBIT-UHFFFAOYSA-N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 150000003613 toluenes Chemical class 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical class C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 2
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 150000001451 organic peroxides Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims 5
- 150000002431 hydrogen Chemical group 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 abstract description 83
- 238000005691 oxidative coupling reaction Methods 0.000 abstract description 29
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 abstract description 24
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 abstract description 21
- 229910052742 iron Inorganic materials 0.000 abstract description 10
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 abstract description 5
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N deuterated chloroform Substances [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 239000003208 petroleum Substances 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- 238000005259 measurement Methods 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 13
- 238000001816 cooling Methods 0.000 description 12
- 239000012046 mixed solvent Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 5
- CHLICZRVGGXEOD-UHFFFAOYSA-N 1-Methoxy-4-methylbenzene Chemical compound COC1=CC=C(C)C=C1 CHLICZRVGGXEOD-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- ZBTMRBYMKUEVEU-UHFFFAOYSA-N 1-bromo-4-methylbenzene Chemical compound CC1=CC=C(Br)C=C1 ZBTMRBYMKUEVEU-UHFFFAOYSA-N 0.000 description 2
- MMZYCBHLNZVROM-UHFFFAOYSA-N 1-fluoro-2-methylbenzene Chemical compound CC1=CC=CC=C1F MMZYCBHLNZVROM-UHFFFAOYSA-N 0.000 description 2
- BTQZKHUEUDPRST-UHFFFAOYSA-N 1-fluoro-3-methylbenzene Chemical compound CC1=CC=CC(F)=C1 BTQZKHUEUDPRST-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- WGSZEVOKTCZOEI-UHFFFAOYSA-M 1,3-ditert-butylimidazol-1-ium bromide Chemical compound [Br-].C(C)(C)(C)[N+]1=CN(C=C1)C(C)(C)C WGSZEVOKTCZOEI-UHFFFAOYSA-M 0.000 description 1
- YOVUXLHIVNBVKO-UHFFFAOYSA-N 1-nitro-4-phenylmethoxybenzene Chemical group C1=CC([N+](=O)[O-])=CC=C1OCC1=CC=CC=C1 YOVUXLHIVNBVKO-UHFFFAOYSA-N 0.000 description 1
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 1
- 229910021576 Iron(III) bromide Inorganic materials 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 238000006959 Williamson synthesis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 125000001743 benzylic group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 150000002505 iron Chemical class 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229960003540 oxyquinoline Drugs 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2265—Carbenes or carbynes, i.e.(image)
- B01J31/2269—Heterocyclic carbenes
- B01J31/2273—Heterocyclic carbenes with only nitrogen as heteroatomic ring members, e.g. 1,3-diarylimidazoline-2-ylidenes
-
- 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
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/29—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of oxygen-containing functional groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles 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 in position 2
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/46—C-H or C-C activation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0225—Complexes comprising pentahapto-cyclopentadienyl analogues
- B01J2531/0233—Aza-Cp ligands, i.e. [CnN(5-n)Rn]- in which n is 0-4 and R is H or hydrocarbyl, or analogous condensed ring systems
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/842—Iron
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing aryl benzyl ether compounds, namely, the aryl benzyl ether compounds have a molecular formula of [ (A)tBuNCH=CHNtBu)CH][FeBr4]The iron (III) complex containing 1, 3-di-tert-butyl imidazole cation is used as a catalyst, di-tert-butyl peroxide is used as an oxidant, and the corresponding aryl benzyl ether compound is synthesized through the oxidative coupling reaction of a phenolic compound and a toluene compound. The method is the first example of preparing the aryl benzyl ether compound by the oxidative coupling reaction of the phenolic compound and the toluene compound by using the iron-based catalyst, and has atom economy, environmental friendliness and good substrate applicability.
Description
Technical Field
The invention belongs to the technical field of preparation of organic compounds, and particularly relates to a novel preparation method of an aryl benzyl ether compound.
Background
The aryl benzyl ether is widely existed in medical molecules as an important structural fragment, is also an important organic synthesis intermediate, and can be used for synthesizing medicines, dyes, spices and the like. The traditional method for preparing such compounds is the Williamson synthesis, which requires the use of toxic and polluting halogenated hydrocarbons and strong bases. Therefore, the development of a new method with atom economy and environmental friendliness for synthesizing the compound has strong practical application value. Examples of drug molecules containing aryl benzyl ether structural fragments are as follows:
in recent decades, transition metal catalyzed carbon-hydrogen (C-H) bond functionalization reactions have become a new approach to the construction of carbon-carbon (C-C) and carbon-hetero (C-X) bonds, which avoids the pre-synthesis and use of halogenated hydrocarbons and thus is very atom economical and environmentally friendly. In recent years, oxidative coupling reactions involving carboxylic acids have been used to construct C (sp)3) the-O bond has been studied greatly, and provides a new method for synthesizing carboxylic ester compounds. However, involving an oxidative coupling reaction involving less acidic phenolic compounds to construct C (sp)3) Reports of-O bonds are rare. In 2012, the Reddy group used copper acetate as a catalyst and tert-butyl peroxide as an oxidant, and first realized that phenolic compounds were ortho-positioned to the oxygen atom by C (sp)3) -oxidative coupling of H bonds (see: kumar, G.S., Pieber, B., Reddy, K.R., kappa, C.O., a,Chem. Eur. J. 2012, 18, 6124). In 2013, the Patel group tried oxidative coupling reaction of phenolic compounds and toluene compounds with copper acetate hydrate as catalyst and tert-butyl peroxide as oxidant, and the expected target product was aryl benzyl ether compound, but the final product was phenolic ester compound, which is caused by unstable and rapid oxidation of the intermediate aryl benzyl ether compound into phenolic ester compound (see: Saroj, K. R.; Srimanta G.; Arghya, B.; Anupal, G.; Nilufa, K.; Patel, B. K.),Org. Lett. 2013, 15, 4106）。
iron is one of the most abundant metals on the earth, and has the advantages of low price, easy obtainment, good biocompatibility and the like. At present, phenolic compounds and C (sp) related to iron-based catalysts3) The oxidative coupling reaction of-H bond is only one example. Wu Yongchang subject group in 2014 with Fe2(CO)9Is used as a catalyst, tert-butyl peroxide is used as an oxidant, and the ortho-position C (sp) of the phenolic compound and the oxygen atom is realized3-H) oxidative coupling of bonds (see: barve, B, D, Wu, Y, C, Koriek, M, Cheng, Y, Wang, J, Chang, F, R.Org. Lett. 2014, 16, 1912）。
So far, no literature report on constructing aryl benzyl ether compounds by catalyzing oxidative coupling reaction of phenolic compounds and toluene compounds by using iron catalysts is found.
Disclosure of Invention
The invention aims to provide a new method for synthesizing aryl benzyl ether compounds, namely, aryl benzyl ether compounds with molecular formula [ ()tBuNCH=CHNtBu)CH][FeBr4]The iron (III) complex containing 1, 3-di-tert-butyl imidazole cation is used as a catalyst, di-tert-butyl peroxide is used as an oxidant, and the corresponding aryl benzyl ether compound is synthesized through the oxidative coupling reaction of a phenolic compound and a toluene compound. [(tBuNCH=CHNtBu)CH][FeBr4]Is a simple and easily obtained iron (III) complex with definite structure and air stability.
In order to achieve the purpose of the invention, the technical scheme adopted by the invention is as follows:
a method for synthesizing aryl benzyl ether compounds comprises the steps of taking a phenolic compound and a toluene compound as raw materials, and reacting in the presence of a catalyst and an organic oxidant to obtain aryl benzyl ether compounds;
the chemical structural formula of the catalyst is as follows:
in the invention, the chemical structural formula of the toluene compound is as follows:
r is hydrogen, methoxy, halogen;
R2hydrogen and methyl.
The phenolic compound is a compound with hydroxyl connected on an aromatic ring or a heteroaromatic ring, such as phenol, substituted phenol, hydroxypyridine, hydroxyquinoline and hydroxybenzothiazole; the chemical structural formula of the phenol and the substituted phenol is as follows:
R1the substituent is alkyl, nitro, trifluoromethyl, acetoxy, halogen or acetyl, and the alkyl is methyl or tert-butyl. Such as 4-nitrophenol, 4-trifluoromethylphenol, 4-acetoxyphenol, 2, 6-dichlorophenol, 2-acetylphenol, phenol, 4-methylphenol, 4-tert-butylphenol.
In the technical scheme, benzene compounds are used as a reaction substrate and a solvent, and the molar ratio of a catalyst to a phenol compound to an organic oxidant is (0.05-0.10) to 1 to (0.5-1.5); preferably 0.10: 1: 1.5.
In the technical scheme, the reaction temperature is 90-140 ℃ and the reaction time is 15-40 hours; the reaction temperature is preferably 110-130 ℃ and the reaction time is 20-30 hours.
In the technical scheme, after the reaction is finished, the reaction product is cooled to room temperature, the product is purified by column chromatography, and the aryl benzyl ether compound is obtained by taking a mixed solvent of ethyl acetate and petroleum ether in volume ratio as a developing agent.
In the above technical solution, the organic oxidant is an organic peroxide, such as di-tert-butyl peroxide.
The reaction process of the present invention can be represented as follows:
due to the application of the technical scheme, the invention has the following advantages:
1. the invention realizes the oxidative coupling of the phenolic compound and the toluene compound by taking the iron (III) complex as the catalyst for the first time. This is the first example of a phenolic compound with the benzylic C (sp)3) The oxidative coupling reaction of the-H bond provides a new method for synthesizing aryl benzyl ether compounds. Compared with the existing synthesis method, the method has better atom economy, avoids using toxic and polluting halogenated hydrocarbon and strong alkali, and accords with the development concept of green synthetic chemistry.
2. The iron catalyst adopted by the invention has the advantages of definite structure, simple synthesis and stable air, shows good catalytic activity and is beneficial to large-scale industrial synthesis application.
Detailed Description
All the raw materials of the invention are commercial products, and the specific preparation method and the test method are the conventional techniques in the field. The invention is further described below with reference to the following examples:
the first embodiment is as follows: containing 1, 3-di-tert-butyl imidazole cation (molecular formula [ () (tBuNCH=CHNtBu)CH][FeBr4]) Synthesis of iron (III) complexes of
1, 3-Di-tert-butylimidazolium bromide (0.26 g, 1.0 mmol) was added to iron tribromide (0.27G, 0.9 mmol) in tetrahydrofuran, 60 oCThe reaction is carried out for 24 hours, the solvent is pumped out in vacuum, hexane is washed, the solvent is pumped out, tetrahydrofuran is used for extraction, the clear solution is centrifuged and transferred, hexane is added into the clear solution for recrystallization, and reddish brown solid powder is separated out at room temperature, and the yield is 91%.
The chemical structural formula is as follows:
elemental analysis of the product resulted in the following:
iron complexes are not characterized as being nuclear magnetic due to their paramagnetic properties.
Complex [ () (tBuNCH=CHNtBu)CH][FeBr4]In the form of ion pairs, in which [ FeBr ]4]-It was characterized by Raman spectroscopy and was found to be at 204 cm-1Characteristic peaks are observed, and are consistent with the reports in the literature (Melissa, S.; Eric, R. S.; Eric, V. P.; Freeman, R. G.), Inorg. Chem., 2001, 40, 2298）。
cationic moiety of the complex [ ((iii))tBuNCH=CHNtBu)CH]+The molecular ion peak is observed at 181.1699, theoretically 181.1699, and is consistent with theory.
The obtained compound was confirmed to be the objective compound.
Example two: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 4-nitrophenol with toluene
4-Nitrophenol (69.5 mg, 0.5 mmol), catalyst (28 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), toluene (4.5 mL) were added sequentially to the flask at 130 deg.CoReaction under C for 24 hoursIn the meantime, after the reaction was completed, the reaction mixture was cooled to room temperature, and the product was purified by column chromatography (using a mixed solvent of ethyl acetate and petroleum ether in a volume ratio of 1: 10 as a developing solvent), whereby the yield was 89%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3, TMS): 8.29 - 8.17 (m, 2H), 7.48 - 7.37 (m, 5H), 7.08 -7.00 (m, 2H), 5.19 (s, 2H)。
the product is p-nitrophenyl benzyl ether:
replacing the iron catalyst with 20 mol% copper powder, and obtaining no target product (trace) under the same other conditions; the iron catalyst was replaced with 60 mol% copper powder, and di-t-butyl peroxide was increased to 1.0 mmol, but the other conditions were unchanged, and the target product (trace) was not obtained.
Example three: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 4-trifluoromethylphenol with toluene
4-Trifluoromethylphenol (81.05 mg, 0.5 mmol), catalyst (28 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), toluene (4.5 mL) were added sequentially to the flask at 130 deg.CoAnd C, reacting for 24 hours, cooling to room temperature after the reaction is finished, and purifying the product by column chromatography (with petroleum ether as a developing agent) with the yield of 86%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3, TMS): 7.53 (d, J = 8.7 Hz, 2H), 7.45 - 7.30 (m, 5H), 7.01 (d, J = 8.7 Hz, 2H), 5.08 (s, 2H).
example four: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 4-acetoxyphenol with toluene
4-Acetoxyphenol (76.07 mg, 0.5 mmol), catalyst (28 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), toluene (4.5 mL) were added to the flask in succession at 130. mu.l oCThe reaction is carried out for 24 hours, the reaction is cooled to room temperature after the reaction is finished, and the product is purified by column chromatography (using a mixed solvent with the volume ratio of ethyl acetate to petroleum ether of 1: 10 as a developing solvent), and the yield is 82%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3, TMS): 8.03 - 7.97 (m, 2H), 7.45 - 7.33 (m, 5H), 7.00 (dd, J = 8.5, 1.3 Hz, 2H), 5.12 (s, 2H), 3.89 (d, J = 0.9 Hz, 3H).
example five: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 2, 6-dichlorophenol with toluene
2, 6-dichlorophenol (81.5 mg, 0.5 mmol), catalyst (28 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), toluene (4.5 ml) were added sequentially to the reaction flask at 130. mu.l oCThe reaction is carried out for 24 hours, the reaction is cooled to room temperature after the reaction is finished, and the product is purified by column chromatography (by taking petroleum ether as a developing agent) with the yield of 81 percent.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3, TMS): 7.65-7.59 (m, 2H), 7.48-7.32 (m, 5H), 7.07-7.00 (m, 1H), 5.09 (s, 2H).
example six: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 2-acetylphenol with toluene
2-Acetylphenol (60.0. mu.l, 0.5 mmol), catalyst (28 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), toluene (4.5 ml) were added sequentially to the reaction flask at 130. mu.l oCReacting for 24 hours, cooling to room temperature after the reaction is finished, and purifying the product by column chromatography (a), (b)A mixed solvent of ethyl acetate and petroleum ether in a volume ratio of 1: 5 is used as a developing solvent), and the yield is 80%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3, TMS): 7.73 (dd, J = 7.8, 1.9 Hz, 1H), 7.40 - 7.22 (m, 6H), 6.95 - 6.87 (m, 2H), 5.02 (s, 2H), 2.53 (s, 3H).
example seven: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of phenol with toluene
Phenol (44.0. mu.l, 0.5 mmol), catalyst (22 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), toluene (4.5 ml) were added sequentially to the reaction flask at 130. mu.l oCThe reaction is carried out for 24 hours, the reaction is cooled to room temperature after the reaction is finished, and the product is purified by column chromatography (by taking petroleum ether as a developing agent) with the yield of 80 percent.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3, TMS): 7.44 - 7.24 (m, 7H), 6.99 - 6.91 (m, 3H), 5.03 (s, 2H)。
the iron catalyst was replaced with 20 mol% Cu (OAc)2Otherwise, the target product (trace) was not obtained.
Example eight: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 4-methylphenol with toluene
4-Methylphenol (54.07 mg, 0.5 mmol), catalyst (22 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), toluene (4.5 ml) were added sequentially to the flask at 130 deg.CoAnd C, reacting for 24 hours, cooling to room temperature after the reaction is finished, and purifying the product by column chromatography (using a mixed solvent with the volume ratio of ethyl acetate to petroleum ether of 1: 10 as a developing agent) to obtain the yield of 79 percent.
The product was dissolved in CDCl3Medium (about 0.4 mL), seal the tube, at room temperature in Unity Inova-Characterization by measurement on a type 400 NMR instrument:1H NMR (400 MHz, CDCl3, TMS): 7.64 - 7.45 (m, 5H), 7.29 - 7.24 (m, 2H), 7.10 - 7.04 (m, 2H), 5.18 (s, 2H), 2.47 (s, 3H).
example nine: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 4-tert-butylphenol with toluene
4-Tert-butylphenol (75.1 mg, 0.5 mmol), catalyst (22 mg, 0.05 mmol), di-t-butyl peroxide (140. mu.l, 0.75 mmol), toluene (4.5 ml) were added sequentially to the flask at 130 deg.CoAnd C, reacting for 24 hours, cooling to room temperature after the reaction is finished, and purifying the product by column chromatography (with petroleum ether as a developing agent) to obtain the yield of 75%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3, TMS): δ 7.47 - 7.32 (m, 7H), 6.97 - 6.93 (m, 2H), 5.07 (s, 2H), 1.33 (s, 9H).
example ten: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 2-hydroxypyridine with toluene
2-Hydroxypyridine (47.6 mg, 0.5 mmol), catalyst (42 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), toluene (4.5 ml) were added sequentially to the reaction flask at 130 deg.CoAnd C, reacting for 24 hours, cooling to room temperature after the reaction is finished, and purifying the product by column chromatography (with petroleum ether as a developing agent) to obtain the yield of 78%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3, TMS): 7.35 - 7.26 (m, 6H), 6.63 - 6.57 (m, 1H), 6.12 (td, J = 6.7, 1.4 Hz, 1H), 5.13 (s, 2H).
example eleven: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 8-hydroxyquinoline with toluene
Sequentially adding into a reaction bottle8-Hydroxyquinoline (72.6 mg, 0.5 mmol), catalyst (42 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), toluene (4.5 mL) at 130oAnd C, reacting for 24 hours, cooling to room temperature after the reaction is finished, and purifying the product by column chromatography (with petroleum ether as a developing agent) to obtain the yield of 75%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3, TMS): 8.77 (dd, J = 4.2, 1.6 Hz, 1H), 8.12 (d, J= 1.6 Hz, 1H), 7.41 - 7.27 (m, 8H), 7.23 - 7.18 (m, 1H), 4.26 (s, 2H).
the iron catalyst was replaced with 20 mol% copper powder, and di-t-butyl peroxide was increased to 1.0 mmol, but the other conditions were unchanged, and the target product (trace) was not obtained.
Example twelve: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 2-hydroxybenzothiazoles with toluene
2-hydroxybenzothiazole (75.6 mg, 0.5 mmol), catalyst (42 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), toluene (4.5 ml) were added sequentially to the reaction flask at 130. mu.loAnd C, reacting for 24 hours, cooling to room temperature after the reaction is finished, and purifying the product by column chromatography (using a mixed solvent with the volume ratio of ethyl acetate to petroleum ether of 1: 30 as a developing agent) to obtain the yield of 68%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3, TMS): δ 7.42 (dd, J = 7.7, 1.3 Hz, 1H), 7.35 - 7.18 (m, 6H), 7.15 - 7.10 (m, 1H), 6.95 (dd, J = 8.0, 1.2 Hz, 1H), 5.15 (s, 2H).
example thirteen: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 4-nitrophenol with ethylbenzene
4-nitrophenol (69.5 mg, 0.5 mmol) was added to the flask in sequence and catalyzedAgent (28 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), toluene (4.5 ml) at 130oAnd C, reacting for 24 hours, cooling to room temperature after the reaction is finished, and purifying the product by column chromatography (using a mixed solvent with the volume ratio of ethyl acetate to petroleum ether of 1: 50 as a developing agent) to obtain the yield of 79 percent.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): δ 8.10 - 8.03 (m, 2H), 7.36 - 7.23 (m, 5H), 6.93 - 6.86 (m, 2H), 5.39 (q, J = 6.5 Hz, 1H), 1.67 (d, J = 6.4 Hz, 3H).
example fourteen: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling reaction of 4-nitrophenol and p-methoxytoluene
4-Nitrophenol (69.5 mg, 0.5 mmol), catalyst (28 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), p-methoxytoluene (4.5 ml) were added sequentially to the flask at 130 deg.CoAnd C, reacting for 24 hours, cooling to room temperature after the reaction is finished, and purifying the product by column chromatography (using a mixed solvent with the volume ratio of ethyl acetate to petroleum ether of 1: 20 as a developing agent) to obtain the yield of 96%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): δ 8.19 (d, J = 9.3 Hz, 2H), 7.35 (d, J = 8.7 Hz, 2H), 6.97 (dd, J = 31.0, 9.0 Hz, 4H), 5.08 (s, 2H), 3.82 (s, 3H).
example fifteen: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 4-nitrophenol with 3-fluorotoluene
4-Nitrophenol (69.5 mg, 0.5 mmol), catalyst (28 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), 3-fluorotoluene (4.5 mL) were added sequentially to the flask at 130 deg.CoC, reacting for 24 hours, and cooling to the temperature ofAt room temperature, the product was purified by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether in a volume ratio of 1: 20 as a developing solvent) at a yield of 90%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): δ 8.26 - 8.15 (m, 2H), 7.41 - 7.34 (m, 1H), 7.17 (dd, J = 20.2, 8.5 Hz, 2H), 7.08 - 6.99 (m, 3H), 5.16 (s, 2H).
example sixteen: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 4-nitrophenol with 2-fluorotoluene
4-Nitrophenol (69.5 mg, 0.5 mmol), catalyst (28 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), 2-fluorotoluene (4.5 mL) were added sequentially to the flask at 130 deg.CoAnd C, reacting for 24 hours, cooling to room temperature after the reaction is finished, and purifying the product by column chromatography (using a mixed solvent with the volume ratio of ethyl acetate to petroleum ether being 1: 20 as a developing agent) to obtain the yield of 93 percent.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): δ 8.26 - 8.15 (m, 2H), 7.41 - 7.34 (m, 1H), 7.17 (dd, J = 20.2, 8.5 Hz, 2H), 7.08 - 6.99 (m, 3H), 5.16 (s, 2H).
example seventeen: [(tBuNCH=CHNtBu)CH][FeBr4]Catalyzed oxidative coupling of 4-nitrophenol with 4-bromotoluene
4-Nitrophenol (69.5 mg, 0.5 mmol), catalyst (28 mg, 0.05 mmol), di-tert-butyl peroxide (140. mu.l, 0.75 mmol), 4-bromotoluene (4.5 ml) were added sequentially to the flask at 130 deg.CoAnd C, reacting for 24 hours, cooling to room temperature after the reaction is finished, and purifying the product by column chromatography (using a mixed solvent of ethyl acetate and petroleum ether in a volume ratio of 1: 50 as a developing agent) to obtain the yield of 91%.
The product was dissolved in CDCl3Medium (about 0.4 mL),closing the tube, and determining and characterizing on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): δ8.21 - 8.10 (m, 2H), 7.46 (dd, J = 9.3, 2.5 Hz, 2H), 7.23 (d, J = 8.1 Hz, 2H), 7.00 - 6.89 (m, 2H), 5.03 (s, 2H).
the invention synthesizes the aryl benzyl ether compound by the oxidative coupling reaction of the phenolic compound and the toluene compound under the catalysis of the iron catalyst for the first time, has strong application prospect, and can provide a new method with atom economy and environmental friendliness for the synthesis of the compounds.
Claims (10)
1. A method for synthesizing aryl benzyl ether compounds is characterized in that phenolic compounds and toluene compounds are used as raw materials and react in the presence of a catalyst and an organic oxidant to obtain aryl benzyl ether compounds;
the chemical structural formula of the catalyst is as follows:
2. the method for synthesizing aryl benzyl ether compounds as claimed in claim 1, wherein the molar ratio of the catalyst, the phenolic compound and the organic oxidant is (0.05-0.10) to 1 to (0.5-1.5).
3. The method for synthesizing aryl benzyl ether compounds according to claim 1, wherein the reaction temperature is 90-140 ℃ and the reaction time is 15-40 hours.
4. The method for synthesizing arylbenzyl ether compounds according to claim 3, wherein the reaction temperature is 110 ℃ and 130 ℃ and the reaction time is 20-30 hours.
5. The method for synthesizing aryl benzyl ether compounds according to claim 1, wherein the reaction is completed, and then the reaction product is cooled to room temperature, and the product is purified by column chromatography to obtain aryl benzyl ether compounds.
6. The method for synthesizing aryl benzyl ether compounds according to claim 1, wherein the toluene compounds have the following chemical formula:
r is hydrogen, methoxy, halogen; r2Hydrogen and methyl.
7. The method for synthesizing arylbenzyl ether compounds according to claim 1, wherein the phenolic compound is phenol, substituted phenol, hydroxyquinoline, or hydroxybenzothiazole.
8. The method for synthesizing arylbenzyl ether compounds according to claim 7, wherein the substituted phenol has the following chemical formula:
R1alkyl, nitro, trifluoromethyl, acetoxy, halogen or acetyl.
9. The method for synthesizing arylbenzyl ether compounds according to claim 8, wherein the substituted phenol is 4-nitrophenol, 4-trifluoromethylphenol, 4-acetoxyphenol, 2, 6-dichlorophenol, 2-acetylphenol, 4-methylphenol, or 4-tert-butylphenol.
10. The method for synthesizing arylbenzyl ether compounds according to claim 1, wherein the organic oxidant is an organic peroxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110090038.2A CN112645821A (en) | 2021-01-22 | 2021-01-22 | Method for synthesizing aryl benzyl ether compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110090038.2A CN112645821A (en) | 2021-01-22 | 2021-01-22 | Method for synthesizing aryl benzyl ether compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112645821A true CN112645821A (en) | 2021-04-13 |
Family
ID=75370631
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110090038.2A Pending CN112645821A (en) | 2021-01-22 | 2021-01-22 | Method for synthesizing aryl benzyl ether compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112645821A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113321575A (en) * | 2021-06-15 | 2021-08-31 | 南开大学 | Preparation method of benzyl aryl ether and application of benzyl aryl ether in synthesis |
| CN113717033A (en) * | 2021-09-07 | 2021-11-30 | 嘉兴学院 | Benzyl ether compound and synthesis method thereof |
| WO2022155932A1 (en) * | 2021-01-22 | 2022-07-28 | 苏州大学 | Application of cationic iron(iii) complex containing 1,3-di-tert-butylimidazolium in synthesizing arylbenzyl ether compounds |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20170026843A (en) * | 2015-08-31 | 2017-03-09 | 영남대학교 산학협력단 | Direct Oxidative Arylation of C(sp3)-H Bonds Adjacent to Oxygen of Ethers and Alcohols |
| CN109232265A (en) * | 2018-10-22 | 2019-01-18 | 苏州大学 | A method of preparing benzyl aminated compounds |
| CN109320434A (en) * | 2018-10-22 | 2019-02-12 | 苏州大学 | Ionic iron (III) complex is preparing the application in benzyl aminated compounds as catalyst |
| CN112694375B (en) * | 2021-01-22 | 2023-02-24 | 苏州大学 | Application of iron (III) complex containing 1,3-di-tert-butylimidazole cation in synthesis of aryl benzyl ether compounds |
-
2021
- 2021-01-22 CN CN202110090038.2A patent/CN112645821A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20170026843A (en) * | 2015-08-31 | 2017-03-09 | 영남대학교 산학협력단 | Direct Oxidative Arylation of C(sp3)-H Bonds Adjacent to Oxygen of Ethers and Alcohols |
| CN109232265A (en) * | 2018-10-22 | 2019-01-18 | 苏州大学 | A method of preparing benzyl aminated compounds |
| CN109320434A (en) * | 2018-10-22 | 2019-02-12 | 苏州大学 | Ionic iron (III) complex is preparing the application in benzyl aminated compounds as catalyst |
| CN112694375B (en) * | 2021-01-22 | 2023-02-24 | 苏州大学 | Application of iron (III) complex containing 1,3-di-tert-butylimidazole cation in synthesis of aryl benzyl ether compounds |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022155932A1 (en) * | 2021-01-22 | 2022-07-28 | 苏州大学 | Application of cationic iron(iii) complex containing 1,3-di-tert-butylimidazolium in synthesizing arylbenzyl ether compounds |
| CN113321575A (en) * | 2021-06-15 | 2021-08-31 | 南开大学 | Preparation method of benzyl aryl ether and application of benzyl aryl ether in synthesis |
| CN113321575B (en) * | 2021-06-15 | 2023-05-26 | 南开大学 | Preparation method of benzyl aryl ether and application of benzyl aryl ether in synthesis |
| CN113717033A (en) * | 2021-09-07 | 2021-11-30 | 嘉兴学院 | Benzyl ether compound and synthesis method thereof |
| CN113717033B (en) * | 2021-09-07 | 2024-03-15 | 嘉兴学院 | Benzyl ether compound and synthesis method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112694375B (en) | Application of iron (III) complex containing 1,3-di-tert-butylimidazole cation in synthesis of aryl benzyl ether compounds | |
| CN112645821A (en) | Method for synthesizing aryl benzyl ether compound | |
| Coetzee et al. | Homogeneous catalytic hydrogenation of amides to amines | |
| Tamizh et al. | Ruthenium (II) carbonyl complexes containing ‘pincer like’ONS donor Schiff base and triphenylphosphine as catalyst for selective oxidation of alcohols at room temperature | |
| England et al. | Catalyst Stability Determines the Catalytic Activity of Non‐Heme Iron Catalysts in the Oxidation of Alkanes | |
| Dupé et al. | Activation of molecular oxygen by a molybdenum complex for catalytic oxidation | |
| Sutradhar et al. | Cd (ii) coordination compounds as heterogeneous catalysts for microwave-assisted peroxidative oxidation of toluene and 1-phenylethanol | |
| Zeng et al. | Synthesis and characterization of novel chiral bidentate P, N-containing ligands and ruthenium (II) complex. The application in asymmetric transfer hydrogenation of ketones | |
| Maurya et al. | Molybdenum complexes with a μ-O {MoO 2} 2 core: their synthesis, crystal structure and application as catalysts for the oxidation of bicyclic alcohols using N-based additives | |
| Naganawa et al. | Cu (II)-catalyzed enantioselective oxygen atom transfer from oxaziridine to oxindole derivatives with chiral phenanthroline | |
| Sahli et al. | Preparation of chiral ruthenium (iv) complexes and applications in regio-and enantioselective allylation of phenols | |
| Dai et al. | Construction of Acyclic All‐Carbon Quaternary Stereocenters and 1, 3‐Nonadjacent Stereoelements via Organo/Metal Dual Catalyzed Asymmetric Allenylic Substitution of Aldehydes | |
| CN109433260B (en) | Application of catalyst in synthesis of cyanomethyl carboxylate | |
| WO2022155936A1 (en) | Method for synthesizing aryl benzyl ether compound | |
| Nebra et al. | Intermolecular Alkene Aziridination: An Original and Efficient CuI··· CuI Dinuclear Catalyst Deriving from a Phospha‐Amidinate Ligand | |
| Hao et al. | Ruthenium carbonyl complexes with pyridine-alkoxide ligands: synthesis, characterization and catalytic application in dehydrogenative oxidation of alcohols | |
| CN114478351B (en) | Method for synthesizing alpha-alkyl substituted indole-3-formaldehyde compound | |
| Ayad et al. | Mononuclear iron (II) complexes containing a tripodal and macrocyclic nitrogen ligand: Synthesis, reactivity and application in cyclohexane oxidation catalysis | |
| CN108101755B (en) | Method for preparing chiral 4- (2-propargyl) phenol compound | |
| Lv et al. | The synthesis of novel tetradentate ligands derived from salen and their application in enantioselective silylcyanation of aldehydes | |
| Yang et al. | Preparation of hydrido [CNC]-pincer cobalt complexes via selective C–H/C–F bond activation and their catalytic performances | |
| WO2022155932A1 (en) | Application of cationic iron(iii) complex containing 1,3-di-tert-butylimidazolium in synthesizing arylbenzyl ether compounds | |
| Das et al. | A novel quinoline-based NNN-pincer Cu (ii) complex as a superior catalyst for oxidative esterification of allylic C (sp 3)–H bonds | |
| CN109836457A (en) | A kind of high steric-hindrance amino chirality P, N, N ligand and its preparation method and application | |
| Gao et al. | Preparation and use of polymer‐supported chiral ruthenium complex catalyst |
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 |