CN111548269B - Preparation method of diaryl methane structural compound - Google Patents

Preparation method of diaryl methane structural compound Download PDF

Info

Publication number
CN111548269B
CN111548269B CN202010353253.2A CN202010353253A CN111548269B CN 111548269 B CN111548269 B CN 111548269B CN 202010353253 A CN202010353253 A CN 202010353253A CN 111548269 B CN111548269 B CN 111548269B
Authority
CN
China
Prior art keywords
reaction tube
reaction
mmol
ferrocene
diphenylphosphine
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.)
Active
Application number
CN202010353253.2A
Other languages
Chinese (zh)
Other versions
CN111548269A (en
Inventor
舒兴中
郭鹏
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lanzhou University
Original Assignee
Lanzhou University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Lanzhou University filed Critical Lanzhou University
Priority to CN202010353253.2A priority Critical patent/CN111548269B/en
Publication of CN111548269A publication Critical patent/CN111548269A/en
Application granted granted Critical
Publication of CN111548269B publication Critical patent/CN111548269B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • 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
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms
    • 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
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
    • 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
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/307—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • 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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • 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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/55—Acids; Esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/54—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F17/00—Metallocenes
    • C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic Table
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/0805—Compounds with Si-C or Si-Si linkages comprising only Si, C or H atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/0825—Preparations of compounds not comprising Si-Si or Si-cyano linkages
    • C07F7/083—Syntheses without formation of a Si-C bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/22—Tin compounds
    • C07F7/2208—Compounds having tin linked only to carbon, hydrogen and/or halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/06—One of the condensed rings being a six-membered aromatic ring the other ring being four-membered

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Catalysts (AREA)
  • Indole Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a preparation method of a diaryl methane structural compound. The preparation method of the invention is shown as the formula I:

Description

Preparation method of diaryl methane structural compound
Technical Field
The invention relates to a preparation method of a compound, in particular to a preparation method of a compound with a diaryl methane structure.
Background
Diarylmethanes are ubiquitous building blocks for many drug molecules and functional organic materials, have many unique properties, and are often used as subunit units of supramolecular structure, such as: macrocyclic, interlinked, rotaxane, and the like. With the advent of high-throughput chemistry, a more practical and convenient method for synthesizing various diaryl-containing compounds is needed.
The synthesis of diarylmethane compounds has long been dependent on Friedel-Crafts reaction of aromatic compounds with benzyl electrophiles (rscoadv., 2014,4,28317.). The method is suitable for the benzylation reaction of electron-rich aromatic hydrocarbon, and is difficult to realize for electron-deficient aromatic hydrocarbon; at the same time, regioselective control of the reaction has remained elusive to date. In recent years, with the rise of transition metal catalytic reaction, a feasible approach is provided for realizing the precise synthesis of the diaryl methane compound by the transition metal catalytic coupling reaction. Currently, studies in this area have made long-standing progress in all three areas (chem. Soc. Rev.,2008,37,290). (1) Coupling reaction of aryl metal reagent and benzyl halohydrocarbon and the like; (2) Coupling reaction of aryl electrophile and benzyl metal reagent; (3) And (3) the reductive coupling reaction of the aryl electrophile and the benzyl electrophile. However, these methods all require the preparation of an organometallic reagent, a benzyl halohydrocarbon, or the like in advance. The reagent has high activity and is difficult to preserve for a long time; the preparation process can greatly reduce the compatibility of the functional groups of the reaction, thereby limiting the practicability of the reaction; in addition, the preparation of benzyl halohydrocarbon is accompanied by the generation of a large amount of halogen-containing waste, and is harmful to the environment. The benzyl alcohol and aryl electrophile are large amounts of commercial raw materials, have the characteristics of various types, stability, easy availability and the like, and can be introduced in the later stage of complex compound synthesis very simply. The synthesis of the diaryl methane compound by taking the benzyl alcohol and the aryl electrophile as raw materials has important theoretical significance and reagent application value. However, this synthetic strategy has yet to be developed. The only successful case requires the use of equivalent amounts of titanium complex as an activator for the alcohol and is mainly applicable to the conversion of iodo aromatic hydrocarbons. (org. Lett.2018,20,7846.)
Disclosure of Invention
The invention provides a preparation method for a diaryl methane structural compound, and the strategy provides a method for synthesizing the diaryl compound, which is direct, efficient and good in compatibility with functional groups.
The preparation method of the diaryl methane structural compound is shown as a formula I, namely under the catalysis of nickel,
1,1' -bis (diphenylphosphine) ferrocene and 1, 10-phenanthroline are used as ligands, dimethyl oxalate is used as an additive, manganese powder is used as a reducing agent, and benzyl alcohol and an aryl electrophile react to prepare a target compound under the condition that N, N-Dimethylformamide (DMF) is used as a solvent, wherein the ring A is any one of benzene ring, furan ring, thiophene ring, pyridine ring, indole ring or ferrocene, and the ring B is benzene ring or pyridine ring; r is R 1 ，R 2 Each independently represents alkyl or substituted alkyl or aryl or substituted aryl at different positions, and X represents any one of chlorine, bromine, iodine or trifluoro methane sulfonate.
Preferably the diarylmethane structural compounds of the present invention are prepared as follows:
target compound 4- (furan-2-ylmethyl) methyl benzoate, 0.02mmol of nickel (II) bromide diethylene glycol dimethyl ether complex, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.02mmol of 1, 10-phenanthroline, 0.02mmol of pyridine, 0.02mmol of aluminum trichloride, 0.36mmol of dimethyl oxalate and 0.6mmol of manganese powder are sequentially added into a reaction tube, then 1mL of DMF solution dissolved with 0.2mmol of furfuryl alcohol and 0.3mmol of 4- (trifluoromethylsulfonyloxy) methyl benzoate is injected into the reaction tube, the reaction tube is closed, the reaction tube is reacted for 30 hours under the condition of inert gas protection, water quenching is carried out after the reaction is finished, the reaction tube is extracted with ethyl acetate, anhydrous sodium sulfate is dried, then filtration and concentration are carried out, and the concentrate is subjected to silica gel column chromatography to obtain 4- (furan-2-ylmethyl) methyl benzoate.
The target compound is 4- (benzo [ b ] thiophene-2-ylmethyl) methyl benzoate, and the preparation method comprises the following steps: to the reaction tube were successively added 0.02mmol of nickel (II) bromide diethylene glycol dimethyl ether complex, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.02mmol of 1, 10-phenanthroline, 0.02mmol of pyridine, 0.02mmol of aluminum trichloride, 0.36mmol of dimethyl oxalate, 0.6mmol of manganese powder, then 1mL of DMF solution in which 0.2mmol of 1-benzothiophene-2-methanol and 0.3mmol of methyl 4- (trifluoromethanesulfonyl) benzoate were dissolved was poured into the reaction tube, the reactor was closed, reacted under inert gas protection for 30 hours at 80℃and quenched with water after the reaction was completed, extracted with ethyl acetate, dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on silica gel to obtain the objective compound.
The target compound is 4- (pyridin-3-ylmethyl) benzoic acid methyl ester, and the preparation method is as follows: to the reaction tube were successively added 0.02mmol of nickel (II) bromide diethylene glycol dimethyl ether complex, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.02mmol of 1, 10-phenanthroline, 0.02mmol of pyridine, 0.02mmol of aluminum trichloride, 0.36mmol of dimethyl oxalate, 0.6mmol of manganese powder, then 1mL of DMF solution in which 0.2mmol of indole-7-methanol and 0.3mmol of methyl 4- (trifluoromethanesulfonyl) benzoate were dissolved was poured into the reaction tube, the reaction tube was closed, the reaction was allowed to react at 80℃under inert gas protection for 30 hours, after the reaction was completed, quenched with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on silica gel to give the target compound.
The target compound was methyl 4- ((1H-indol-7-yl) methyl) benzoate, prepared as: to the reaction tube were successively added 0.02mmol of nickel (II) bromide diethylene glycol dimethyl ether complex, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.02mmol of 1, 10-phenanthroline, 0.02mmol of pyridine, 0.02mmol of aluminum trichloride, 0.36mmol of dimethyl oxalate, 0.6mmol of manganese powder, then 1mL of DMF solution in which 0.2mmol of indole-7-methanol and 0.3mmol of methyl 4- (trifluoromethanesulfonyl) benzoate were dissolved was poured into the reaction tube, the reaction tube was closed, reacted at 80℃under inert gas protection for 30 hours, after the reaction was completed, quenched with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was subjected to silica gel column chromatography to obtain methyl 4- ((1H-indol-7-yl) benzoate.
The target compound is 4- ((ferrocenyl) methyl benzoate, and the preparation method comprises the following steps: 0.02mmol of nickel (II) bromide diethylene glycol dimethyl ether compound, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.02mmol of 1, 10-phenanthroline, 0.02mmol of pyridine, 0.02mmol of aluminum trichloride, 0.36mmol of dimethyl oxalate, 0.6mmol and manganese powder are sequentially added into a reaction tube, 1mL of DMF solution dissolved with 0.2mmol of indole-7-methanol and 0.3mmol of 4- (trifluoromethanesulfonyl) methyl benzoate is injected into the reaction tube, the reaction tube is closed, the reaction is carried out at 80 ℃ under the inert gas protection condition, after the reaction is finished, the mixture is quenched with water, extracted with ethyl acetate, dried with anhydrous sodium sulfate, filtered and concentrated, and the concentrate is subjected to silica gel column chromatography to obtain 4- ((ferrocenyl) methyl) benzoate.
The target compound is 4- (4- (tributylstannyl) benzyl) methyl benzoate, and the preparation method comprises the following steps: to the reaction tube, 0.02mmol of (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.004mmol of 1, 10-phenanthroline, 0.36mmol of dimethyl oxalate, 0.6mmol of manganese powder were sequentially added, and then a solution of DMF (1 mL) in which 0.2mmol of 4- (tributyltin) benzyl alcohol and 0.3mmol of 4- (trifluoromethylsulfonyloxy) benzoic acid methyl ester were dissolved was poured into the reaction tube, the reaction tube was closed, reacted at 80℃under inert gas protection for 30 hours, quenched with water after the completion of the reaction, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was chromatographed on a silica gel column to obtain 4- (4- (tributyltin alkyl) benzyl) benzoic acid methyl ester.
The target compound is 6- (4-methoxybenzyl) -1H-indole, and the preparation method comprises the following steps: to a clean and dry reaction tube, 0.02mmol of (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride, 0.02mmol of 1' -bis (diphenylphosphine) ferrocene, 0.004mmol of 1, 10-phenanthroline, 0.36mmol of dimethyl oxalate, 0.6mmol of manganese powder were sequentially added, and then a solution of DMF (1 mL) in which 0.2mmol of methoxybenzyl alcohol and 0.3mmol of 6-chloroindole were dissolved was poured into the reaction tube, the reaction tube was closed, reacted for 30 hours at 80℃under inert gas protection, quenched with water after the reaction was completed, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was chromatographed on a silica gel column to give 6- (4-methoxybenzyl) -1H-indole.
The target compound is 2- (4-methoxybenzyl) -4, 6-dimethylpyridine and the preparation method comprises the following steps: to the reaction tube were successively added 0.02mmol of (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.004mmol of 1, 10-phenanthroline, 0.02mmol of aluminum trichloride, 0.36mmol of dimethyl oxalate, 0.6mmol of manganese powder, then 1mL of DMF solution in which 0.2mmol of p-methoxybenzyl alcohol and 0.3mmol of 2-chloro-4, 6-dimethylpyridine were dissolved was poured into the reaction tube, the reaction tube was closed, the reaction was allowed to proceed under inert gas protection at 80℃for 30 hours, after the completion of the reaction, quenched with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on a silica gel column to give 2- (4-methoxybenzyl) -4, 6-dimethylpyridine.
The target compound is 3a, and the preparation method is shown as a formula II:
to a clean, dry, 100mL round bottom flask equipped with a stirrer was added, in order, 0.25mmol of nickel (II) bromide diethylene glycol dimethyl ether complex, 0.25mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.25mmol of 1, 10-phenanthroline, 0.25mmol of pyridine, 10mmol of dimethyl oxalate, 15mmol of manganese powder, 200mgMolecular sieves, then 7.5mmol (4- (trimethylsilyl) benzyl alcohol and 5mmol of compound 2a in formula II in 25mL DMF are dissolved in the reaction tube, the round bottom flask is closed, the reaction is carried out at 80 ℃ for 40h under inert gas protection, after the reaction is finished, the quenching is carried out with water, extraction is carried out with ethyl acetate, drying is carried out with anhydrous sodium sulfate, filtration and concentration are carried out, and the concentrate is subjected to silica gel column chromatography to obtain the product 3a.
The invention provides a synthetic method for efficiently synthesizing a diaryl methane structure. The method takes low-cost and easily-obtained benzyl alcohol and aryl electrophile as raw materials, and realizes the construction of the diaryl methane structure through the catalysis process of a low-cost nickel catalyst. The practicability of the reaction substrate is wide, wherein chlorinated, brominated and iodized aromatic hydrocarbon and aryl sulfonate can be coupled with benzyl alcohol to obtain a target product; the reaction selectivity is unique, and the method is suitable for preparing a plurality of metal-substituted diaryl methane compounds such as B, si, sn and the like; the reaction condition is mild, and most of active functional groups can be compatible; the reaction can be carried out on a gram-scale while being suitable for the post-modification of complex bioactive molecules containing substrate-like structures. These advantages make the invention highly practical for the synthesis of diarylmethane structures.
Drawings
FIG. 1 shows the hydrogen spectrum of Compound 3a in deuterated chloroform using 400M nuclear magnetism 1 H NMR(400MHz,CDCl 3 ))；
FIG. 2 shows the carbon spectrum of Compound 3a in deuterated chloroform using 400M nuclear magnetism 13 C NMR(100MHz,CDCl 3 ))；
Detailed Description
The following description of the preferred embodiments of the present invention is provided for the purpose of illustration and explanation only and is not intended to limit the present invention.
Example 1
The reaction is shown in the formula 1, takes 2-methylbenzyl alcohol and 4- (trifluoromethanesulfonyl oxygen) methyl benzoate as raw materials,
in a glove box filled with inert gas, nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added to a clean and dry reaction tube, then a solution of DMF (1 mL) in which 2-methylbenzyl alcohol (22.4 mg,0.2 mmol) and 4- (trifluoromethylsulfonyloxy) methyl benzoate (85.2 mg,0.3 mmol) were dissolved was poured into the reaction tube, a plug was plugged, the solution was taken out from the glove box, reacted at 80℃for 30 hours under inert gas protection, after the reaction was completed, extracted with water (30 mL. Times.3), dried over sodium sulfate, and then filtered and concentrated, and the concentrate was eluted with 200 to 300 mesh ethyl benzoate (200 mL of ethyl benzoate, 50mL of ethyl benzoate, i.50 mL of ethyl benzoate was obtained. (colorless oily liquid, 34.7mg, yield 72%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.96-7.93(m,2H),7.20-7.15(m,5H),7.11-7.08(m,1H),4.03(s,2H),3.89(s,3H),2.21(s,3H). 13 C NMR(100MHz,CDCl 3 )δ167.2,146.1,138.1,136.8,130.6,130.1,129.9,128.8,128.1,126.9,126.3,52.2,39.7,19.8.HRMS(ESI):[M+H] + calcd.for C 16 H 17 O 2 241.1223,found 241.1219.。
example 2
The reaction is shown in the formula 2, 3, 4-dimethoxy benzyl alcohol and 4- (trifluoromethanesulfonyl oxy) methyl benzoate are used as raw materials,
In a glove box filled with inert gas, nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added to a clean and dry reaction tube, then a solution of DMF (1 mL) in which 3, 4-dimethoxybenzyl alcohol (33.6 mg,0.2 mmol) and 4- (trifluoromethylsulfonyloxy) methyl benzoate (85.2 mg,0.3 mmol) were dissolved was poured into the reaction tube, a plug was plugged, taken out of the glove box, reacted at 80℃for 30h under inert gas protection, after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was eluted with 200 mL of silica gel (200 mL of ethyl benzoate, 50mL of ethyl benzoate, 4-methoxybenzoate, i.50 mL of ethyl benzoate was obtained. (colorless oily liquid, 34.9mg, 61% yield).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.97-7.95(m,2H),7.26-7.24(m,2H),6.80(d,J＝8.0Hz,1H),6.71(dd,J 1 ＝8.4Hz,J 2 ＝2.0Hz,1H),6.67(d,J＝2.0Hz,1H),3.97(s,2H),3.90(s,3H),3.86(s,3H),3.82(s,3H). 13 C NMR(100MHz,CDCl 3 )δ167.2,149.2,147.8,146.9,132.8,129.9,128.9,128.2,121.1,112.4,111.5,56.1,56.0,52.1,41.6.HRMS(ESI):[M+H] + calcd.for C 17 H 19 O 4 287.1278,found 287.1281.。
example 3
The reaction is shown in the formula 3, wherein piperitol and 4- (trifluoromethanesulfonyl oxy) methyl benzoate are taken as raw materials and are dried cleanly in a glove box filled with inert gas
Nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.04 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (.2 mg,0.6 mmol) were added sequentially to a dry reaction tube, then a solution of piperonyl alcohol (30.4 mg,0.2 mmol) and methyl 4- (trifluoromethanesulfonyl) benzoate (85.2 mg,0.3 mmol) in DMF (1 mL) was injected into the reaction tube, a plug was plugged, taken out of the glove box under inert gas protection conditions, reacted for 30h at 80 ℃, after the reaction was completed, quenched with water, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was chromatographed on silica gel column (200-300 mesh, ethyl acetate=50 mL) to obtain 4- (50 mL of benzene: 50 mL) as petroleum ether ][1,3]Dioxa-5-ylmethyl) benzoic acid methyl ester. (colorless oily liquid, 40.5mg, 75% yield).
The product detection data are as follows:
1 H NMR(600MHz,CDCl 3 )δ7.95(d,J＝8.4Hz,2H),7.23(d,J＝8.4Hz,2H),6.74(d,J＝7.8Hz,1H),6.65-6.63(m,2H),5.91(s,2H),3.93(s,2H),3.89(s,3H). 13 C NMR(150MHz,CDCl 3 )δ167.1,147.9,146.7,146.2,134.0,129.9,128.9,128.2,121.9,109.5,108.4,101.0,52.1,41.7.HRMS(ESI):[M+H] + calcd.for C 16 H 15 O 4 271.0965,found 271.0966.。
example 4
The reaction is shown in a formula 4, 3, 4-difluorobenzyl alcohol and 4- (trifluoromethanesulfonyl oxy) methyl benzoate are taken as raw materials in a glove box filled with inert gas,
to a clean and dry reaction tube was added sequentially (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.04 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol), then a solution of 3, 4-difluorobenzyl alcohol (28.8 mg,0.2 mmol) and methyl 4- (trifluoromethylsulfonyloxy) benzoate (85.2 mg,0.3 mmol) in DMF (1 mL) was poured into the reaction tube, the stopper was plugged, the reaction tube was taken out of the glove box, reacted for 30 hours under inert gas protection, after the reaction was completed, quenched with water, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on silica gel (200 to 300 mesh, eluting with ethyl acetate (1 mL: ethyl acetate: 50mL of 4-benzyl benzoate) to obtain 4-difluorobenzyl benzoate). (colorless oily liquid, 27.3mg, yield 52%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.99-7.97(m,2H),7.24-7.22(m,2H),7.12-7.05(m,1H),6.98-6.87(m,2H),3.98(s,2H),3.91(s,3H). 13 C NMR(150MHz,CDCl 3 )δ167.0,150.7(dd,J 1 ＝247.5Hz,J 2 ＝12.0Hz),149.3(dd,J 1 ＝244.5Hz,J 2 ＝12.0Hz),145.5,137.2(t,J＝4.5Hz),130.2,129.0,128.7,124.9(t,J＝4.5Hz),117.9(d,J＝16.5Hz),117.4(d,J＝18.0Hz),52.2,41.2. 19 F NMR(376MHz,CDCl 3 )δ-137.66(d,J＝21.1Hz),-141.24(d,J＝21.4Hz).HRMS(ESI):[M+H] + calcd.for C 15 H 13 F 2 O 2 263.0878,found 263.0874.。
Example 5
The reaction is shown in the formula 5, and takes 4- (hydroxymethyl) benzonitrile and 4- (trifluoromethanesulfonyl oxy) methyl benzoate as raw materials in a glove box
To a clean and dry reaction tube was added successively (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.04 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol), and then a solution of 4- (hydroxymethyl) benzonitrile (26.6 mg,0.2 mmol) and methyl 4- (trifluoromethanesulfonyl) benzoate (85.2 mg,0.3 mmol) in DMF (1 mL) was poured into the reaction tube, the stopper was plugged, taken out of the glove box, reacted for 30 hours at 80℃under inert gas protection, after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on silica gel (200 to 300 mesh ethyl acetate, ethyl benzonitrile=20 mL of 4-cyano benzoate was obtained as a silica gel. (colorless oily liquid, 32.6mg, 65% yield).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ8.00-7.97(m,2H),7.61-7.58(m,2H),7.29-7.23(m,4H),4.09(s,2H),3.91(s,3H). 13 C NMR(100MHz,CDCl 3 )δ167.0,145.8,144.7,132.6,130.2,129.8,129.1,128.8,119.0,110.5,52.3,42.0.HRMS(ESI):[M+H] + calcd.for C 16 H 14 NO 2 252.1019,found 252.1015.。
example 6
The reaction is shown in a formula 6, and furfuryl alcohol and 4- (trifluoromethanesulfonyl oxy) methyl benzoate are taken as raw materials in a glove box
To a clean and dry reaction tube was added sequentially nickel (II) bromide diethylene glycol dimethyl ether complex (7.1 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (3.6 mg,0.02 mmol), pyridine (1.6 mg,0.02 mmol), aluminum trichloride (2.7 mg,0.02 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol), and then a DMF (1 mL) solution in furfuryl alcohol (19.6 mg,0.2 mmol) and methyl 4- (trifluoromethanesulfonyl) benzoate (85.2 mg,0.3 mmol) was poured into the reaction tube, a plug was plugged, the reaction tube was taken out of the glove box, reacted at 80 ℃ for 30h under inert gas protection, after the reaction was completed, extracted with water (30 ml×3), anhydrous sodium sulfate was dried, and then a silica gel solution was filtered and concentrated to obtain a solution of ethyl furan acetate (200-50 mL), which was a concentrated to obtain a solution of ethyl furan acetate (200-50 mL). (colorless oily liquid, 36mg, yield 83%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.97(d,J＝8.4Hz,2H),7.334-7.327(m,1H),7.29(d,J＝8.4Hz,2H),6.31-6.29(m,1H),6.03-6.02(m,1H),4.02(s,2H),3.90(s,3H). 13 C NMR(100MHz,CDCl 3 )δ167.1,153.6,143.6,141.9,130.0,128.9,128.7,110.5,106.8,52.2,34.6.HRMS(ESI):[M+H] + calcd.for C 13 H 13 O 3 217.0859,found 217.0855.。
example 7
The reaction is shown in formula 7, and is carried out by using 1-benzothiophene-2-methanol and 4- (trifluoromethanesulfonyl oxy) benzoic acid methyl ester
To a clean and dry reaction tube, a solution of nickel (II) bromide in diethylene glycol dimethyl ether (7.1 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (3.6 mg,0.02 mmol), pyridine (1.6 mg,0.02 mmol), aluminum trichloride (2.7 mg,0.02 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) was sequentially added, and then a solution of 1-benzothiophene-2-methanol (32.8 mg,0.2 mmol) and 4- (trifluoromethanesulfonyl) methyl benzoate (85.2 mg,0.3 mmol) in DMF (1 mL) was injected into the reaction tube, the plug was plugged, the reaction tube was taken out from the glove box, reacted at 80 ℃ for 30h under inert gas protection conditions, ethyl acetate (30×3 mL) was used, ethyl acetate was used, and aqueous solution was concentrated to obtain 200-300 mL of ethyl benzoate (200 mL, 50mL, aqueous sodium benzoate was eluted), and then concentrated to obtain 200-50 mL of ethyl benzoate (ethyl benzoate, ethyl acetate was eluted by chromatography, and aqueous solution was concentrated to obtain 200-50 mL. (white solid, melting point: 95-96 ℃ C.; 42.3mg, 75% yield).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ8.02-7.99(m,2H),7.76-7.73(m,1H),7.68-7.66(m,1H),7.37-7.24(m,4H),7.02-7.01(m,1H),4.28(s,2H),3.91(s,3H). 13 C NMR(100MHz,CDCl 3 )δ167.0,144.9,143.9,140.1,140.0,130.1,128.9,128.86,124.4,124.0,123.2,122.3,122.2,52.2,37.0.HRMS(ESI):[M+H] + calcd.for C 17 H 15 O 2 S 283.0787,found 283.0778.。
Example 8
The reaction is shown in formula 8, and takes 3-pyridine methyl alcohol and 4- (trifluoromethanesulfonyl oxygen) methyl benzoate as raw materials
In a glove box, nickel (II) bromide (7.1 mg,0.02 mmol) of diethylene glycol dimethyl ether complex, 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (3.6 mg,0.02 mmol), pyridine (1.6 mg,0.02 mmol), aluminum trichloride (2.7 mg,0.02 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added to a clean and dry reaction tube, then a solution of DMF (1 mL) in which 3-pyridinemethanol (21.8 mg,0.2 mmol) and 4- (trifluoromethanesulfonyl) methyl benzoate (85.2 mg,0.3 mmol) were dissolved was poured into the reaction tube, a plug was plugged, the reaction tube was taken out from the glove box, reacted at 100 ℃ for 30h under inert gas protection conditions, quenched with water after the reaction was completed, extracted with ethyl acetate (30 ml×3), anhydrous sodium sulfate was then dried, and the solution was concentrated to obtain 200-300 mL of ethyl acetate as a silica gel chromatography, and a solution of 200-10 mL of ethyl benzoate, which was a solution of ethyl acetate, and then a concentration was eluted. (colorless oily liquid, 32.2mg, 71% yield).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ8.51-8.48(m,2H),7.98(d,J＝8.0Hz,2H),7.47-7.44(m,1H),7.26-7.21(m,3H),4.04(s,2H),3.91(s,3H).
13 C NMR(100MHz,CDCl 3 )δ167.0,150.3,148.1,145.2,136.5,135.7,130.1,129.0,128.6,123.7,52.2,39.1.HRMS(ESI):[M+H] + calcd.for C 14 H 14 NO 2 228.1019,found 228.1017.。
example 9
The reaction is shown in the formula 9, and indole-7-methanol and 4- (trifluoromethanesulfonyl oxy) methyl benzoate are used as raw materials
In a glove box, nickel (II) bromide (7.1 mg,0.02 mmol) of diethylene glycol dimethyl ether complex, 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (3.6 mg,0.02 mmol), pyridine (1.6 mg,0.02 mmol), aluminum trichloride (2.7 mg,0.02 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) and a solution of methyl 4- (trifluoromethanesulfonyl) benzoate (85.2 mg,0.3 mmol) in DMF (1 mL) were sequentially added to a clean and dry reaction tube, the solution was poured into the reaction tube, a plug was plugged, the solution was taken out of the glove box, the reaction was quenched with water after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3 mmol), anhydrous sodium sulfate was dried, and a concentrate of indole-7-methanol (29.4 mg,0.2 mmol) and a concentrate of 4- (trifluoromethanesulfonyl) benzoic acid was obtained as a silica gel as a chromatography-ethyl acetate solution (1 mL, 200 mL of ethyl acetate, and a concentrate was eluted. (colorless oily liquid, 40.3mg, 76% yield).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.95(d,J＝8.4Hz,2H),7.87(s,1H),7.58(d,J＝8.0Hz,1H),7.30(d,J＝8.4Hz,2H),7.12-7.09(m,2H),7.04-7.02(m,1H),6.55-6.54(m,1H),4.28(s,2H),3.89(s,3H). 13 C NMR(150MHz,CDCl 3 )δ167.1,145.3,135.0,130.2,128.8,128.7,128.3,124.3,123.1,122.2,120.2,119.8,103.2,52.2,38.4.HRMS(ESI):[M+Na] + calcd.for C 17 H 15 NNaO 2 288.0995,found 288.0991.。
example 10
The reaction is shown in formula 10, and ferrocenyl methanol and 4- (trifluoromethanesulfonyl oxy) methyl benzoate are used as raw materials
In a glove box filled with inert gas, nickel (II) bromide, diethylene glycol dimethyl ether complex (7.1 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (3.6 mg,0.02 mmol), pyridine (1.6 mg,0.02 mmol), aluminum trichloride (2.7 mg,0.02 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added to a clean and dry reaction tube, then a solution of indole-7-methanol (29.4 mg,0.2 mmol) and 4- (trifluoromethanesulfonyl) methyl benzoate (85.2 mg,0.3 mmol) in DMF (1 mL) was injected into the reaction tube, a plug was plugged, the reaction was taken out of the glove box under air-protecting conditions, the reaction was quenched with water at 80 ℃ for 30h, ethyl acetate (30×3 mL), and then water was dried to obtain 200 mL of ethyl acetate, and then a concentrate of ethyl acetate, i.300 mL of ethyl benzoate, i.e., a solution was eluted as silica gel. (pale yellow oily liquid, 41.1mg, yield 62%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.95-7.93(m,2H),7.25-7.23(m,2H),4.12-4.08(m,9H),3.89(s,3H),3.74(s,2H). 13 C NMR(100MHz,CDCl 3 )δ167.2,147.0,129.8,128.5,128.0,87.0,68.8,68.7,67.8,52.1,36.2.HRMS(ESI):[M+Na] + calcd.for C 19 H 18 FeNaO 2 357.0548,found 357.0546.。
example 11
The reaction is shown in formula 11, and is carried out by 3- (trimethylsilyl) benzyl alcohol and 4- (trifluoromethanesulfonyl oxy) benzoic acid methyl ester
The ester was fed as a starting material into a glove box filled with inert gas, to a clean and dry reaction tube was added successively (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.04 mmol),molecular sieves (30 mg), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol), and DMF (1 mL) in which 3- (trimethylsilyl) benzyl alcohol (36 mg,0.2 mmol) and methyl 4- (trifluoromethylsulfonyloxy) benzoate (85.2 mg,0.3 mmol) were dissolved were poured into a reaction tube, a plug was plugged, and the tube was taken out of the glove box, reacted at 80℃for 30 hours under inert gas protection, quenched with water after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was chromatographed on a silica gel column (200 to 300 mesh silica gel, eluent petroleum ether: ethyl acetate=50 mL:1 mL) to obtain methyl 4- (3- (trimethylsilyl) benzyl) benzoate. (colorless oily liquid, 49.5mg, yield 83%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.97-7.95(m,2H),7.39-7.34(m,2H),7.29-7.23(m,3H),7.13-7.11(m,1H),4.03(s,2H),3.88(s,3H),0.25(s,9H). 13 C NMR(100MHz,CDCl 3 )δ167.2,146.7,141.0,139.4,134.0,131.5,129.9,129.5,129.1,128.2,128.1,52.1,42.2,-1.0.HRMS(ESI):[M+H] + calcd.for C 18 H 23 O 2 Si 299.1462,found 299.1451.。
example 12
The reaction is shown in formula 12, and is carried out by using 4- (trimethylsilyl) benzyl alcohol and 4- (trifluoromethanesulfonyl oxy) benzoic acid methyl ester
The ester was fed as a starting material into a glove box filled with inert gas, to a clean and dry reaction tube was added successively (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.04 mmol),molecular sieves (30 mg), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) then dissolved 4- (trimethylsilyl) benzyl alcohol (36 mg,0.2 mmol) and methyl 4- (trifluoromethylsulfonyloxy) benzoate (85.2 mg,0.3 mmol)) DMF (1 mL) solution of (2) was poured into the reaction tube, the plug was plugged, taken out of the glove box, reacted at 80℃for 30 hours under inert gas protection, quenched with water after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was purified by silica gel column chromatography (200-300 mesh silica gel, eluent petroleum ether: ethyl acetate=50 mL:1 mL) to obtain methyl 4- (4- (trimethylsilyl) benzyl) benzoate. (colorless oily liquid, 42.9mg, yield 72%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.97-7.94(m,2H),7.47-7.45(m,2H),7.27(d,J＝8.4Hz,2H),7.17(d,J＝7.6Hz,2H),4.02(s,2H),3.90(s,3H),0.25(s,9H). 13 C NMR(100MHz,CDCl 3 )δ167.2,146.5,140.8,138.3,133.8,130.0,129.1,128.5,128.2,52.2,42.0,-0.97.HRMS(ESI):[M+Na] + calcd.for C 18 H 22 NaO 2 Si 321.1281,found 321.1280.。
example 13
The reaction is shown in formula 13 as 4- (hydroxymethyl) phenylboronic acid pinacol ester and 4- (trifluoromethanesulfonyl oxy) benzene
Methyl formate was used as a starting material in a glove box filled with inert gas, nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added to a clean and dry reaction tube, then a solution of 4- (hydroxymethyl) phenylboronic acid pinacol ester (xxmg, 0.2 mmol) and 4- (trifluoromethanesulfonyl) methyl benzoate (85.2 mg,0.3 mmol) in DMF (1 mL) was poured into the reaction tube, a plug was plugged, the solution was taken out of the glove box, the solution was reacted at 80℃for 30h under inert gas protection, after the reaction was completed, extracted with water (30 mL. Times.3), dried over anhydrous sodium sulfate, and then the solution was filtered and concentrated to give 4- (2.20 mL) ethyl 4- (hydroxymethyl) phenylboronic acid pinacol, 4-methylbenzoyl) and 4- (2 mL) benzyl acetate as a silica gel chromatography concentrate. (colorless oily liquid, 49.3mg, yield 70%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.96-7.94(m,2H),7.76-7.74(m,2H),7.25-7.18(m,4H),4.04(s,2H),3.90(s,3H),1.33(s,12H). 13 C NMR(100MHz,CDCl 3 )δ167.2,146.4,143.5,135.3,130.0,129.1,128.6,128.2,83.9,52.2,42.2,25.0. 11 B NMR(192MHz,CDCl 3 )δ30.19.HRMS(ESI):[M+Na] + calcd.for C 21 H 25 BNaO 4 375.1738,found 375.1739.。
example 14
The reaction is shown in FIG. 14 as 4- (tributyltin) benzyl alcohol and 4- (trifluoromethanesulfonyl) oxy) benzoic acid methyl ester
In a raw material tank, 1 '-bis (diphenylphosphine) ferrocene (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol), and then a solution of 4- (tributyltin) benzyl alcohol (79.6 mg,0.2 mmol) and 4- (trifluoromethylsulfonyloxy) methyl benzoate (85.2 mg,0.3 mmol) in DMF (1 mL) were sequentially added to a clean and dry reaction tube, a plug was plugged, the mixture was taken out from the glove box, reacted at 80℃for 30h, after the end of the reaction, extracted with ethyl acetate (30 mL. Times 3), dried over anhydrous sodium sulfate, and then the concentrate was eluted with 200 mL of ethyl benzoate (20 mL of ethyl benzoate as a solution containing 200 mL of tributyltin acetate as a solution, and a solution of 4- (tributyltin acetate) as a chromatography column chromatography (200 mL of 4-benzyltin acetate). (colorless oily liquid, 66mg, 64% yield).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.97-7.94(m,2H),7.44-7.33(m,2H),7.27-7.24(m,2H),7.15-7.11(m,2H),4.00(s,2H),3.89(s,3H),1.60-1.45(m,6H),1.37-1.27(m,6H),1.12-0.95(m,6H),0.88(t,J＝7.2Hz,9H). 13 C NMR(100MHz,CDCl 3 )δ167.2,146.7,139.9,139.6,136.9,129.9,129.1,128.7,128.2,52.1,42.1,29.2,27.5,13.8,9.7.HRMS(ESI):[M+H] + calcd.for C 27 H 41 O 2 Sn 517.2123,found 517.2121.。
example 15
The reaction is shown in the formula 15, and p-methoxybenzyl alcohol and 4- (trifluoromethanesulfonyl oxy) methyl benzoate are taken as raw materials
In the above, to a reaction tube of a glove box, 1 '-bis (diphenylphosphine) ferrocene (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added, and then a solution of DMF (1 mL) in which p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and methyl 4- (trifluoromethylsulfonyloxy) benzoate (85.2 mg,0.3 mmol) were dissolved was poured into the reaction tube, the stopper was closed, the reaction tube was taken out from the glove box, reacted for 30 hours under inert gas protection, after the reaction was completed, quenched with water, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on a silica gel column (200 to 300 mesh, eluting with ethyl acetate=30 mL of ethyl acetate=4-methyl benzoate, i.4 mL of methoxybenzyl formate was obtained. (colorless oily liquid, 40.4mg, yield 79%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.96-7.94(m,2H),7.23(d,J＝8.0Hz,2H),7.10-7.07(m,2H),6.85-6.82(m,2H),3.96(s,2H),3.88(s,3H),3.77(s,3H). 13 C NMR(100MHz,CDCl 3 )δ167.2,158.2,147.1,132.3,130.0,129.9,128.9,128.0,114.1,55.3,52.1,41.1.HRMS(ESI):[M+H] + calcd.for C 16 H 17 O 3 257.1172,found 257.1169.。
example 16
The reaction is shown in a formula 16, and p-methoxybenzyl alcohol and 4-fluorophenyl trifluoro methane sulfonate are taken as raw materials in a glove box
To a clean and dry reaction tube was successively added (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.04 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol), and then a solution of DMF (1 mL) in which p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and p-transesterification trifluoro methane sulfonate (73.2 mg,0.3 mmol) were dissolved was poured into the reaction tube, the reaction tube was plugged with a plug, taken out of the glove box under inert gas protection, reacted for 30 hours at 80℃and after the reaction was completed, quenched with water, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was chromatographed on silica gel column (200 to 300 mesh, ethyl acetate as petroleum ether, eluting agent: 1mL = 4-methoxybenzyl fluoride) to obtain 1-100 mL of benzene. (colorless oily liquid, 31mg, 72% yield).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.13-7.05(m,4H),6.97-6.93(m,2H),6.85-6.81(m,2H),3.88(s,2H),3.78(s,3H). 13 C NMR(100MHz,CDCl 3 )δ161.5(d,J C-F ＝242.0Hz),158.2,137.4(d,J C-F ＝4.0Hz),133.2,130.27(d,J C-F ＝8Hz),129.9,115.3(d,J C-F ＝22Hz),114.1,55.4,40.3. 19 F NMR(376MHz,CDCl 3 )-117.52.HRMS(ESI):[M+H] + calcd.for C 14 H 14 FO 217.1023,found 217.1020.。
example 17
The reaction is shown in formula 17, and p-methoxybenzyl alcohol and 4- (2-hydroxyethyl) phenyl trifluoro methane sulfonate are used as raw materials
In a glove box filled with inert gas, nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added to a clean and dry reaction tube, then a solution of DMF (1 mL) in which p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and 4- (2-hydroxyethyl) phenyl triflate (81 mg,0.3 mmol) were dissolved was poured into the reaction tube, the stopper was plugged, taken out of the glove box, reacted for 30h at 80℃under inert gas protection, after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on silica gel (200 to 300 mesh, eluting with ethyl acetate=1 mL of 4- (2-hydroxyethyl) phenyl-triflate (1 mL). (colorless oily liquid, 27.2mg, yield 56%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.16-7.09(m,6H),6.85-6.81(m,2H),3.90(s,2H),3.84(q,J＝6.4Hz,2H),3.78(s,3H),2.84(t,J＝6.4Hz,2H),1.34(t,J＝6.0Hz,1H). 13 C NMR(100MHz,CDCl 3 )δ158.0,139.9,136.1,133.4,129.9,129.2,129.1,114.0,63.8,55.4,40.7,38.9.HRMS(ESI):[M+Na] + calcd.for C 16 H 18 NaO 2 265.1199,found 265.1198.。
example 18
The reaction is shown in the formula 18, and takes p-methoxybenzyl alcohol and 4- (morpholinomethyl) phenyl trifluoro methane sulfonate as raw materials
To a reaction tube which was dried by hand, nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added, and then a solution of DMF (1 mL) in which p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and 4- (morpholinomethyl) phenyl triflate (97.5 mg,0.3 mmol) were dissolved was poured into the reaction tube, the plug was plugged, taken out from the glove box, reacted for 30 hours under inert gas protection, after the reaction was completed, quenched with water, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on silica gel (200 to 300 mesh, eluting with ethyl acetate=4- (1 mL) benzyl 4- (4 mL) benzyl) to obtain benzyl morpholine. (colorless oily liquid, 36.2mg, yield 61%).
The product detection data are as follows:
1 H NMR(600MHz,CDCl 3 )δ7.24-7.22(m,2H),7.13-7.08(m,4H),6.84-6.81(m,2H),3.90(s,2H),3.77(s,3H),3.70(t,J＝7.2Hz,4H),3.47(s,2H),2.44(t,J＝7.2Hz,4H). 13 C NMR(150MHz,CDCl 3 )δ158.1,140.7,135.2,133.4,129.9,129.5,128.8,114.0,67.0,63.2,55.4,53.7,40.8.HRMS(ESI):[M+H] + calcd.for C 19 H 24 NO 2 298.1802,found 298.1805.。
example 19
The reaction is shown in formula 19, and p-methoxybenzyl alcohol and p-4- (trimethylsilyl) phenyl trifluoro methane sulfonate are used as raw materials
To a clean and dry reaction tube in a glove box filled with inert gas, nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol), and then a solution of DMF (1 mL) in which p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and 4- (trimethylsilyl) phenyl triflate (89.4 mg,0.3 mmol) were dissolved were sequentially added, the reaction tube was capped with a flip plug, taken out of the glove box, reacted at 80℃for 30h under inert gas protection, after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over sodium sulfate, then filtered and concentrated, and the concentrate was eluted by silica gel chromatography (200 mesh ethyl acetate, 1 mL: 100mL of petroleum ethyl acetate, 4- (trimethylsilyl) to obtain trimethylphenyl ether). (colorless oily liquid, 32.4mg, 60% yield).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.45-7.43(m,2H),7.17(d,J＝7.6Hz,2H),7.13-7.09(m,2H),6.84-6.80(m,2H),3.91(s,2H),3.76(s,3H),0.24(s,9H). 13 C NMR(100MHz,CDCl 3 )δ158.0,142.4,137.7,133.7,133.2,130.0,128.3,114.0,55.3,41.1,-0.93.HRMS(ESI):[M+H] + calcd.for C 17 H 23 OSi 271.1513,found 271.1512.。
example 20
The reaction is shown in the formula 20, using p-methoxybenzyl alcohol and 4-chlorophenol as raw materials, and drying cleanly in a glove box filled with inert gas
Nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added to the dry reaction tube, then a solution of DMF (1 mL) in which p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and 4-chlorophenol (38.4 mg,0.3 mmol) were dissolved was poured into the reaction tube, the stopper was plugged, taken out of the glove box, reacted at 80℃for 30 hours under inert gas protection, quenched with water after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was purified by silica gel column (200 to 300 mesh silica gel, eluent: petroleum ether: ethyl acetate=10 mL:1 mL) to obtain 4- (4-methoxy) phenol. (colorless oily liquid, 25.7mg, 60% yield).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.09-7.02(m,4H),6.83-6.81(m,2H),6.74-6.72(m,2H),4.73-4.69(m,1H),3.84(s,2H),3.77(s,3H). 13 C NMR(100MHz,CDCl 3 )δ158.1,153.9,134.0,133.9,130.1,129.9,115.4,114.1,55.4,40.3.HRMS(ESI):[M+H] + calcd.for C 14 H 15 O 2 215.1067,found 215.1065.。
example 21
The reaction is shown in the formula 21, using p-methoxybenzyl alcohol and 6-chloroindole as raw materials, and drying cleanly in a glove box filled with inert gas
Nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added to the dry reaction tube, and then a solution of DMF (1 mL) in which p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and 6-chloroindole (45.3 mg,0.3 mmol) were dissolved was poured into the reaction tube, the plug was plugged, taken out of the glove box, reacted at 80℃for 30H under inert gas protection, quenched with water after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed over silica gel column (200-300 mesh silica gel, eluent: ethyl acetate=50 mL), to obtain benzyl-1- (4-methoxy) -indole. (colorless oily liquid, 29.9mg, yield 63%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.97(s,1H),7.54(d,J＝8.0Hz,1H),7.14-7.10(m,4H),6.98-6.96(m,1H),6.84-6.80(m,2H),6.50-6.48(m,1H),4.03(s,2H),3.77(s,3H). 13 C NMR(100MHz,CDCl 3 )δ158.1,136.4,135.8,134.2,130.1,126.3,124.0,121.6,120.7,114.0,111.1,102.6,55.4,41.4.HRMS(ESI):[M+H] + calcd.for C 16 H 16 NO 238.1226,found 238.1220.。
example 22
The reaction is shown in formula 22, takes p-methoxybenzyl alcohol and 2-chloro-4, 6-dimethylpyridine as raw materials, and is carried out in a glove box
In a clean and dry reaction tube, (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg)0.004 mmol), aluminum trichloride (2.6 mg,0.02 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol), then a solution of p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and 2-chloro-4, 6-dimethylpyridine (42.3 mg,0.3 mmol) in DMF (1 mL) was poured into the reaction tube, the plug was plugged, taken out of the glove box, reacted for 30h under inert gas protection conditions at 80 ℃, quenched with water after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed over silica gel (200-300 mesh silica gel, eluent being petroleum ether: ethyl acetate=50 mL:1 mL) to obtain 2- (4-methoxybenzyl) -4, 6-dimethylpyridine. (colorless oily liquid, 28.6mg, yield 63%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.19-7.17(m,2H),6.85-6.83(m,2H),6.79(s,1H),6.66(s,1H),4.03(s,2H),3.78(s,3H),2.50(s,3H),2.21(s,3H). 13 C NMR(100MHz,CDCl 3 )δ160.7,158.3,157.6,147.9,132.0,130.3,121.9,121.0,114.1,55.4,43.8,24.4,21.0.HRMS(ESI):[M+H] + calcd.for C 15 H 18 NO 228.1383,found 228.1382.。
example 23
The reaction is shown in the formula 23, which takes p-methoxybenzyl alcohol and 4-bromo-1, 2-methylenedioxybenzene as raw materials, and the raw materials are dried cleanly in a glove box filled with inert gas
Nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.04 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added to the dry reaction tube, then a solution of DMF (1 mL) in which p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and 4-bromo-1, 2-methylenedioxybenzene (60 mg,0.3 mmol) were dissolved was poured into the reaction tube, the plug was plugged, taken out of the glove box under inert gas protection, reacted at 80℃for 30h, after the reaction was completed, quenched with water, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on silica gel column (200 to 300 mesh silica gel)The eluent is petroleum ether, ethyl acetate=100mL:1mL) to obtain 5- (4-methoxybenzyl) benzo [ d ]][1,3]And (3) a bisoxazole. (colorless oily liquid, 36.9mg, yield 82%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.11-7.08(m,2H),6.84-6.82(m,2H),6.74-6.72(m,1H),6.65-6.63(m,2H),5.90(s,2H),3.83(s,2H),3.78(s,3H). 13 C NMR(100MHz,CDCl 3 )δ158.1,147.8,145.9,135.6,133.5,129.9,121.7,114.0,109.4,108.3,100.9,55.4,40.8.HRMS(ESI):[M+H] + calcd.for C 15 H 15 O 3 243.1016,found 243.1020.。
example 24
The reaction is carried out in a glove box filled with inert gas by taking p-methoxybenzyl alcohol and p-bromobenzotrifluoride as raw materials as shown in a formula 24 and drying
Nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added to the reaction tube, then a solution of p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and p-bromobenzotrifluoride (67.2 mg,0.3 mmol) in DMF (1 mL) was poured into the reaction tube, the plug was plugged, the reaction tube was removed from the glove box, the reaction tube was allowed to react for 30h at 80℃under inert gas protection, quenched with water after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on silica gel column (200-300 mesh silica gel, eluent: ethyl acetate=100 mL), to obtain 1-4- (trimethoxybenzyl) benzene. (colorless oily liquid, 29.6mg, yield 56%).
The product detection data are as follows:
1 H NMR(600MHz,CDCl 3 )δ7.52(d,J＝7.8Hz,2H),7.27(d,J＝7.8Hz,2H),7.08(d,J＝8.4Hz,2H),6.85-6.84(m,2H),3.97(s,2H),3.78(s,3H). 13 C NMR(100MHz,CDCl 3 )δ158.3,145.8,132.2,130.0,129.2,128.5(q,J＝32.0Hz),125.5(q,J＝4.0Hz),124.4(q,J＝270.0Hz),114.2,55.4,41.0. 19 F NMR(376MHz,CDCl 3 )δ-62.30.HRMS(ESI):[M+H] + calcd.for C 15 H 14 F 3 O 267.0991,found 267.0987.。
example 25
The reaction is shown in the formula 25, and p-methoxybenzyl alcohol and 4-bromobenzocyclobutene are taken as raw materials, and the raw materials are subjected to clean and dry reaction in a glove box filled with inert gas
Nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.04 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol), and then a solution of DMF (1 mL) in which p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and 4-bromobenzocyclobutene (54.6 mg,0.3 mmol) were dissolved were sequentially added to the tube, the tube was capped with a flip-top plug, taken out of the glove box under inert gas protection conditions, reacted at 80℃for 30h, quenched with water after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, then filtered and concentrated, the concentrate was chromatographed over a silica gel column (200-300 mesh silica gel, eluent being petroleum ether: ethyl acetate=100 mL) to give benzyl 4- (4.0.3 mmol) bicyclo [ 2.0:0 ]]Octa-1, 3, 5-triene. (colorless oily liquid, 35.8mg, yield 80%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.11-7.08(m,2H),7.01(dd,J 1 ＝7.6Hz,J 2 ＝1.6Hz,1H),6.95(dd,J 1 ＝7.6Hz,J 2 ＝1.2Hz,1H),6.87(s,1H),6.84-6.81(m,2H),3.88(s,2H),3.77(s,3H),3.12(s,4H). 13 C NMR(150MHz,CDCl 3 )δ158.2,146.1,143.5,140.4,134.1,129.9,127.5,123.2,122.6,114.1,55.4,41.8,29.5,29.4.HRMS(ESI):[M+H] + calcd.for C 16 H 17 O 225.1274,found 225.1279.。
example 26
The reaction is shown in the formula 26, wherein p-methoxybenzyl alcohol and 2-iodoanisole are taken as raw materials, and the raw materials are put into a clean and dry reaction tube in a glove box filled with inert gas
Nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.04 mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added, then a solution of DMF (1 mL) in which p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and 2-iodoanisole (70.2 mg,0.3 mmol) were dissolved was poured into the reaction tube, a flip plug was plugged, taken out of the glove box, reacted for 30h at 80℃under inert gas protection, quenched with water after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was chromatographed on a silica gel column (200 to 300 mesh silica gel, eluent being petroleum ether: ethyl acetate=100 mL), to obtain 1-isopropyl-2- (4-methoxy) benzyl. (colorless oily liquid, 39.2mg, 86% yield).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.18(td,J 1 ＝8.0Hz,J 2 ＝2.0Hz,1H),7.15-7.11(m,2H),7.05-7.03(m,1H),6.89-6.79(m,4H),3.91(s,2H),3.81(s,3H),3.77(s,3H). 13 C NMR(100MHz,CDCl 3 )δ157.9,157.4,133.2,130.3,130.2,130.0,127.4,120.6,113.8,110.5,55.5,55.4,35.1.HRMS(ESI):[M+H] + calcd.for C 15 H 17 O 2 229.1223,found 229.1218.。
example 27
The reaction is as in formula 27, namely: using p-methoxybenzyl alcohol and 4-chlorobenzoic acid pinacol ester as raw materials, and drying cleanly in a glove box filled with inert gas
Nickel (1, 1 '-bis (diphenylphosphine) ferrocene) dichloride (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added to the reaction tube, then a solution of DMF (1 mL) in which p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and 4-chlorobenzeneboronic acid pinacol ester (71.4 mg,0.3 mmol) were dissolved was poured into the reaction tube, the plug was plugged, taken out of the glove box, reacted at 80℃for 30h under inert gas protection, quenched with water after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3), dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed over silica gel column (200-300 mesh silica gel, eluent: petroleum ether: ethyl acetate=50 mL), to obtain 4- (4, 1-4-methoxy-4-benzyl) -2, 5-dioxa-4, 5-2-methylbenzyl-4-dioxa-5. (colorless oily liquid, 45.4mg, yield 70%).
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.74-7.72(m,2H),7.18(d,J＝7.6Hz,2H),7.09-7.07(m,2H),6.82-6.80(m,2H),3.93(s,2H),3.77(s,3H),1.33(s,12H). 13 C NMR(100MHz,CDCl 3 )δ158.1,145.0,135.1,133.2,130.0,128.5,114.0,83.8,55.4,41.4,25.0. 11 B NMR(192MHz,CDCl 3 )δ30.23.HRMS(ESI):[M+Na] + calcd.for C 20 H 25 BNaO 3 347.1789,found 347.1786.。
example 28
The reaction is shown in formula 28, namely: using p-methoxybenzyl alcohol and 4-bromophenylboronic acid pinacol ester as raw materials, and making the raw materials into gloves
In a tank, 1 '-bis (diphenylphosphine) ferrocene (13.7 mg,0.02 mmol), 1' -bis (diphenylphosphine) ferrocene (11.1 mg,0.02 mmol), 1, 10-phenanthroline (0.7 mg, 0.004mmol), dimethyl oxalate (42.5 mg,0.36 mmol), manganese powder (33.2 mg,0.6 mmol) were sequentially added to a clean and dry reaction tube, and then a solution of DMF (0.5 mL) in which p-methoxybenzyl alcohol (27.6 mg,0.2 mmol) and 4-bromophenylboronic acid pinacol ester (84.6 mg,0.3 mmol) were dissolved was poured into the reaction tube, a flip plug was plugged, taken out of the glove box, reacted at 80℃for 30 hours under inert gas protection, quenched with water after the reaction was completed, extracted with ethyl acetate (30 mL. Times.3) and the solution was not usedDrying with sodium sulfate, filtering, concentrating, and subjecting the concentrate to silica gel column chromatography (200-300 mesh silica gel, eluting with petroleum ether: ethyl acetate=50 mL:1 mL) to obtain 2- (4- (4-methoxybenzyl) phenyl) -4, 5-tetramethyl-1, 3, 2-dioxaborane. (colorless oily liquid, 51.8mg, yield 80%).
The product detection data are as above.
Example 29
The reaction is shown in formula 29, namely: using (4- (trimethylsilyl) benzyl alcohol and compound 2a as raw materials, and making into glove
To a clean, dry, 100mL round bottom flask equipped with a stirrer was added sequentially nickel (II) bromide diethylene glycol dimethyl ether complex (88.3 mg,0.25 mmol), 1' -bis (diphenylphosphine) ferrocene (139 mg,0.25 mmol), 1, 10-phenanthroline (45 mg,0.25 mmol), pyridine (20 mg,0.25 mmol), dimethyl oxalate (1.2 g,10 mmol), manganese powder (823mg, 15 mmol) and the like in a tank>Molecular sieves (200 mg), then a solution of (4- (trimethylsilyl) benzyl alcohol (1.35 mg,7.5 mmol) and compound 2a (2.01 mg,5 mmol) in DMF (25 mL) was poured into the reaction tube, the plug was plugged, taken out of the glove box, reacted at 80 ℃ for 40h under inert gas protection, quenched with water after the reaction was completed, extracted with ethyl acetate (100 ml×3), dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was chromatographed on a silica gel column (200-300 mesh silica gel, eluent petroleum ether: ethyl acetate=50 mL:1 mL) to give the product 3a (colorless oily liquid, 1.06g, yield 51%) as seen in this example as a gram-scale reaction.
The product detection data are as follows:
1 H NMR(400MHz,CDCl 3 )δ7.45-7.43(m,2H),7.21-7.18(m,3H),7.00-6.94(m,2H),3.90(s,2H),2.89-2.85(m,2H),2.53-2.46(m,1H),2.43-2.24(m,2H),2.15-1.94(m,4H),1.61-1.42(m,6H),0.90(s,3H),0.24(s,9H). 13 C NMR(100MHz,CDCl 3 )δ221.1,142.0,138.6,137.8,137.6,136.7,133.7,129.6,128.4,126.5,125.6,50.6,48.1,44.4,41.6,38.4,36.0,31.8,29.5,26.7,25.9,21.7,14.0,-0.94.HRMS(ESI):[M+H] + calcd.for C 28 H 37 OSi 417.2608,found 417.2600.。
finally, it should be noted that: the foregoing description is only a preferred embodiment of the present invention, and the present invention is not limited thereto, but it is to be understood that modifications and equivalents of some of the technical features described in the foregoing embodiments may be made by those skilled in the art, although the present invention has been described in detail with reference to the foregoing embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. A preparation method of a diaryl methane structural compound is characterized by comprising the following steps:
under the catalysis of (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride, 1' -bis (diphenylphosphine) ferrocene and 1, 10-phenanthroline are used as ligands, dimethyl oxalate is used as an additive, manganese powder is used as a reducing agent, N, N-Dimethylformamide (DMF) is used as a solvent, arylmethanol and aryl electrophile react to prepare a target compound, wherein ring A is any one of benzene ring, furan ring, thiophene ring, pyridine ring, indole ring and ferrocene, and ring B is benzene ring or pyridine ring; r is R 1 Is alkyl or substituted alkyl or aryl or substituted aryl at different positions, R 2 Is alkyl or substituted alkyl or aryl or substituted aryl at different sites, and X is any one of chlorine, bromine, iodine or trifluoro methane sulfonate.
2. A preparation method of a diaryl methane structure compound is characterized in that a target compound is methyl 4- (furan-2-ylmethyl) benzoate, 0.02mmol of nickel (II) bromide diethylene glycol dimethyl ether compound, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.02mmol of 1, 10-phenanthroline, 0.02mmol of pyridine, 0.02mmol of aluminum trichloride, 0.36mmol of dimethyl oxalate and 0.6mmol of manganese powder are sequentially added into a reaction tube, 1mL of DMF solution dissolved with 0.2mmol of furfuryl alcohol and 0.3mmol of methyl 4- (trifluoromethylsulfonyloxy) benzoate is injected into the reaction tube, the reaction tube is closed, the reaction tube is reacted for 30h under the condition of inert gas protection, after the reaction is finished, water is quenched, ethyl acetate is used for extraction, anhydrous sodium sulfate is dried, then filtration and concentration are carried out, and the concentrate is subjected to silica gel column chromatography to obtain the methyl 4- (furan-2-ylmethyl) benzoate.
3. A preparation method of a diaryl methane structural compound is characterized in that the prepared target compound is 4- (benzo [ b ] thiophene-2-ylmethyl) methyl benzoate, and the preparation method comprises the following steps: to the reaction tube were successively added 0.02mmol of nickel (II) bromide diethylene glycol dimethyl ether complex, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.02mmol of 1, 10-phenanthroline, 0.02mmol of pyridine, 0.02mmol of aluminum trichloride, 0.36mmol of dimethyl oxalate, 0.6mmol of manganese powder, then 1mL of DMF solution in which 0.2mmol of 1-benzothiophene-2-methanol and 0.3mmol of methyl 4- (trifluoromethanesulfonyl) benzoate were dissolved was poured into the reaction tube, the reaction tube was closed, reacted under inert gas protection at 80℃for 30 hours, after the reaction was completed, quenched with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on silica gel to obtain the objective compound.
4. A preparation method of a diaryl methane structural compound is characterized in that the prepared target compound is 4- (pyridin-3-ylmethyl) methyl benzoate, and the preparation method comprises the following steps: to the reaction tube were successively added 0.02mmol of nickel (II) bromide diethylene glycol dimethyl ether complex, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.02mmol of 1, 10-phenanthroline, 0.02mmol of pyridine, 0.02mmol of aluminum trichloride, 0.36mmol of dimethyl oxalate, 0.6mmol of manganese powder, then 1mL of DMF solution in which 0.2mmol of indole-7-methanol and 0.3mmol of methyl 4- (trifluoromethanesulfonyl) benzoate were dissolved was poured into the reaction tube, the reaction tube was closed, the reaction was allowed to react at 80℃under inert gas protection for 30 hours, after the reaction was completed, quenched with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on silica gel to give the target compound.
5. A preparation method of a diaryl methane structural compound is characterized in that the prepared target compound is 4- ((1H-indol-7-yl) methyl benzoate, and the preparation method comprises the following steps: to the reaction tube were successively added 0.02mmol of nickel (II) bromide diethylene glycol dimethyl ether complex, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.02mmol of 1, 10-phenanthroline, 0.02mmol of pyridine, 0.02mmol of aluminum trichloride, 0.36mmol of dimethyl oxalate, 0.6mmol of manganese powder, then 1mL of DMF solution in which 0.2mmol of indole-7-methanol and 0.3mmol of methyl 4- (trifluoromethanesulfonyl) benzoate were dissolved was poured into the reaction tube, the reaction tube was closed, reacted at 80℃under inert gas protection for 30 hours, after the reaction was completed, quenched with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was subjected to silica gel column chromatography to obtain methyl 4- ((1H-indol-7-yl) benzoate.
6. A preparation method of a diaryl methane structural compound is characterized in that the prepared target compound is 4- ((ferrocenyl) methyl benzoate, and the preparation method comprises the following steps: 0.02mmol of nickel (II) bromide diethylene glycol dimethyl ether compound, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.02mmol of 1, 10-phenanthroline, 0.02mmol of pyridine, 0.02mmol of aluminum trichloride, 0.36mmol of dimethyl oxalate, 0.6mmol and manganese powder are sequentially added into a reaction tube, then 1mL of DMF solution dissolved with 0.2mmol of ferrocene methanol and 0.3mmol of 4- (trifluoromethylsulfonyloxy) methyl benzoate is injected into the reaction tube, the reaction tube is closed, the reaction is carried out for 30 hours under the condition of inert gas protection, after the reaction is finished, the water quenching is carried out, the ethyl acetate extraction is carried out, the anhydrous sodium sulfate drying is carried out, then filtration and concentration are carried out, and the concentrate is subjected to silica gel column chromatography, thus obtaining 4- ((ferrocenyl) methyl) benzoate.
7. A preparation method of a diaryl methane structural compound is characterized in that a target compound is 4- (4- (tributylstannyl) benzyl) methyl benzoate, and the preparation method comprises the following steps: to the reaction tube, 0.02mmol of (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.004mmol of 1, 10-phenanthroline, 0.36mmol of dimethyl oxalate, 0.6mmol of manganese powder were sequentially added, and then a 1mL solution of DMF in which 0.2mmol of 4- (tributyltin) benzyl alcohol and 0.3mmol of 4- (trifluoromethylsulfonyloxy) benzyl benzoate were dissolved was poured into the reaction tube, the reaction tube was closed, reacted at 80℃under inert gas protection for 30 hours, quenched with water after the completion of the reaction, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was chromatographed on a silica gel column to obtain 4- (4- (tributyltin alkyl) benzyl) benzoate.
8. A preparation method of a diaryl methane structural compound is characterized in that a target compound is 6- (4-methoxybenzyl) -1H-indole, and the preparation method comprises the following steps: to a clean and dry reaction tube, 0.02mmol of (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.004mmol of 1, 10-phenanthroline, 0.36mmol of dimethyl oxalate, 0.6mmol of manganese powder were sequentially added, and then 1mL of DM F solution in which 0.2mmol of p-methoxybenzyl alcohol and 0.3mmol of 6-chloroindole were dissolved was injected into the reaction tube, the reaction tube was closed, reacted for 30 hours under inert gas protection at 80℃and quenched with water after the end of the reaction, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was chromatographed on a silica gel column to give 6- (4-methoxybenzyl) -1H-indole.
9. A preparation method of a diaryl methane structural compound is characterized in that a target compound is 2- (4-methoxybenzyl) -4, 6-dimethylpyridine, and the preparation method comprises the following steps: to the reaction tube were successively added 0.02mmol of (1, 1 '-bis (diphenylphosphine) ferrocene) nickel dichloride, 0.02mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.004mmol of 1, 10-phenanthroline, 0.02mmol of aluminum trichloride, 0.36mmol of dimethyl oxalate, 0.6mmol of manganese powder, then 1mL of DMF solution in which 0.2mmol of p-methoxybenzyl alcohol and 0.3mmol of 2-chloro-4, 6-dimethylpyridine were dissolved was poured into the reaction tube, the reaction tube was closed, the reaction was allowed to proceed under inert gas protection at 80℃for 30 hours, after the completion of the reaction, quenched with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, then filtered and concentrated, and the concentrate was chromatographed on a silica gel column to give 2- (4-methoxybenzyl) -4, 6-dimethylpyridine.
10. A preparation method of a diarylmethane structural compound is characterized in that the product is a compound 3a in a formula II, and the preparation method is as shown in the formula II:
to a clean, dry, 100mL round bottom flask equipped with a stirrer was added, in order, 0.25mmol of nickel (II) bromide diethylene glycol dimethyl ether complex, 0.25mmol of 1,1' -bis (diphenylphosphine) ferrocene, 0.25mmol of 1, 10-phenanthroline, 0.25mmol of pyridine, 10mmol of dimethyl oxalate, 15mmol of manganese powder, 200mg of Molecular sieves, then 7.5mmol of (4- (trimethylsilyl) benzyl alcohol and 5mmol of 25mL of DMF solution of compound 2a in formula II were dissolved in the reaction tube, the round bottom flask was closed, reacted at 80 ℃ for 40h under inert gas protection, quenched with water after the reaction, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated, and the concentrate was chromatographed on silica gel to give compound 3a.
CN202010353253.2A 2020-04-29 2020-04-29 Preparation method of diaryl methane structural compound Active CN111548269B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010353253.2A CN111548269B (en) 2020-04-29 2020-04-29 Preparation method of diaryl methane structural compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010353253.2A CN111548269B (en) 2020-04-29 2020-04-29 Preparation method of diaryl methane structural compound

Publications (2)

Publication Number Publication Date
CN111548269A CN111548269A (en) 2020-08-18
CN111548269B true CN111548269B (en) 2023-10-27

Family

ID=72000437

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010353253.2A Active CN111548269B (en) 2020-04-29 2020-04-29 Preparation method of diaryl methane structural compound

Country Status (1)

Country Link
CN (1) CN111548269B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115057776B (en) * 2022-06-15 2023-08-22 必维申瓯质量技术服务温州有限公司 Synthesis method of ethyl 2-naphthoate derivative

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0718265A2 (en) * 1994-12-07 1996-06-26 Research Development Corporation Of Japan Method for producing an alcohol
JP2000256384A (en) * 1999-03-02 2000-09-19 Fuji Chemical Industries Ltd Mew asymmetric ligand
WO2004016594A1 (en) * 2002-08-19 2004-02-26 Sumitomo Chemical Company, Limited Phenylpyridine compound and bactericidal composition containing the same
CN105272792A (en) * 2014-07-14 2016-01-27 中国科学院上海有机化学研究所 Difluoromethylene-containing compound and preparation method thereof
CN106459048A (en) * 2014-05-14 2017-02-22 辉瑞公司 Pyrazolopyridines and pyrazolopyrimidines
CN108101830A (en) * 2018-01-27 2018-06-01 中国科学院成都生物研究所 A kind of preparation method of 3- substitution Oxoindoles and derivative
WO2019052236A1 (en) * 2017-09-15 2019-03-21 大连理工大学 Preparation method for conjugated diene compound
CN109694350A (en) * 2017-10-20 2019-04-30 中国科学院上海有机化学研究所 A kind of compound and preparation method thereof containing methyl fluoride
CN110668913A (en) * 2019-09-16 2020-01-10 江苏三美化工有限公司 Preparation method of trifluoroethyl compound

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8647493B2 (en) * 2012-07-26 2014-02-11 Liquid Light, Inc. Electrochemical co-production of chemicals employing the recycling of a hydrogen halide

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0718265A2 (en) * 1994-12-07 1996-06-26 Research Development Corporation Of Japan Method for producing an alcohol
JP2000256384A (en) * 1999-03-02 2000-09-19 Fuji Chemical Industries Ltd Mew asymmetric ligand
WO2004016594A1 (en) * 2002-08-19 2004-02-26 Sumitomo Chemical Company, Limited Phenylpyridine compound and bactericidal composition containing the same
CN106459048A (en) * 2014-05-14 2017-02-22 辉瑞公司 Pyrazolopyridines and pyrazolopyrimidines
CN105272792A (en) * 2014-07-14 2016-01-27 中国科学院上海有机化学研究所 Difluoromethylene-containing compound and preparation method thereof
WO2019052236A1 (en) * 2017-09-15 2019-03-21 大连理工大学 Preparation method for conjugated diene compound
CN109694350A (en) * 2017-10-20 2019-04-30 中国科学院上海有机化学研究所 A kind of compound and preparation method thereof containing methyl fluoride
CN108101830A (en) * 2018-01-27 2018-06-01 中国科学院成都生物研究所 A kind of preparation method of 3- substitution Oxoindoles and derivative
CN110668913A (en) * 2019-09-16 2020-01-10 江苏三美化工有限公司 Preparation method of trifluoroethyl compound

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
A new approach to access difluoroalkylated diarylmethanes via visible-light photocatalytic cross-coupling reactions;Zhao, YN，et al;《Chemical Communications》;第54卷;3993-3996 *
Nickel catalyzed deoxygenative cross-coupling of benzyl alcohols with aryl-bromides;VinothKumar Chenniappan，et al;《Tetrahedron Letters》;20200212;第61卷(第14期);第1-4页 *
Reductive coupling of benzyl oxalates with highly functionalized alkyl bromides by nickel catalysis;Xiao-Biao Yan，et al;《Chem. Sci》;20180420;第9卷;第4529-4534页 *
咖啡酸酯类衍生物的合成及其生物活性研究;李永胜等;《中草药》;第45卷(第24期);3538-3542 *

Also Published As

Publication number Publication date
CN111548269A (en) 2020-08-18

Similar Documents

Publication Publication Date Title
Yuan et al. Tandem approach to NOBIN analogues from arylhydroxylamines and diaryliodonium salts via [3, 3]-sigmatropic rearrangement
CN112920221B (en) Chiral phosphoric acid with spiro-bis-dihydrobenzothiole skeleton and preparation method and application thereof
CN111548269B (en) Preparation method of diaryl methane structural compound
WO2003018555A1 (en) Process for the preparation of indole derivatives
CN109021003A (en) A kind of vinyl silicon germanium stannane derivative preparation method
CN109896943A (en) A kind of chemical preparation process of cajanin and its analogue
CN108558635B (en) Preparation method of 3-aryl propiolic acid and 3-aryl propiolic acid ester compound
CN111187298B (en) C2-phosphono methylene indole compound and preparation method and application thereof
CN101774874A (en) N-arylating method using pyrrole-2-hydrazide compound as ligand in aqueous phase system
CN116813440A (en) Photocatalytic implementation of C (sp 2 )-C(sp 3 ) Coupling method
CN111777564A (en) Method for synthesizing quinazolinone compound through photocatalytic alcohol oxidation in aqueous phase
CN106995461B (en) A kind of Phosphine ligands of the structure containing benzofuran and its preparation method and application
CN113511970B (en) Synthesis method of aryl substituted alkyne
CN101466718A (en) C2-symmetrical bi-ruthenium dual-phosphine ligand and synthesizing method thereof
CN105209435A (en) Pyridine- or pyrazine-containing compounds
Vignesh et al. Palladium complexes catalyzed regioselective arylation of 2-oxindole via in situ C (sp2)− OH activation mediated by PyBroP
Mešková et al. The development of an approach toward sterically-hindered chiral 2′-aryl-1, 1′-binaphthalenes functionalized at position 2
CN110041355B (en) Method for synthesizing boron-substituted chiral dibenzo-1, 4-aza compounds
Cheng et al. One-Pot Transformation of Hypervalent Iodines into Diversified Phenoxazine Analogues as Promising Photocatalysts
CN111072721B (en) Compound containing bipyrazole ring, intermediate and application thereof
CN107892669A (en) A kind of method by reacting synthesis of quinoline derivatives by means of hydrogen
CN113121543B (en) Preparation method of azepine [4,5-b ] indole compound
CN113861238B (en) Method for synthesizing phosphine chiral center secondary/tertiary phosphine oxide compound through palladium/chiral ligand catalysis
CN112250708B (en) Anthracene-containing dimer skeleton ligand, preparation method thereof and application thereof in metal catalytic reaction
CN111592486B (en) Method for constructing 3,5-disubstituted pyridine by cyclization reaction of aryl ethylene and N, N-dimethylformamide

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
GR01 Patent grant
GR01 Patent grant