CN113443972A - Aryl C-F bond functionalization preparation method - Google Patents

Aryl C-F bond functionalization preparation method Download PDF

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CN113443972A
CN113443972A CN202110727229.5A CN202110727229A CN113443972A CN 113443972 A CN113443972 A CN 113443972A CN 202110727229 A CN202110727229 A CN 202110727229A CN 113443972 A CN113443972 A CN 113443972A
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王雷锋
李曼虹
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Sun Yat Sen University
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    • C07—ORGANIC CHEMISTRY
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    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
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    • C07—ORGANIC CHEMISTRY
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    • C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
    • C07C1/26—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only halogen atoms as hetero-atoms
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
    • C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
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    • C07—ORGANIC CHEMISTRY
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    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/373—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in doubly bound form

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Abstract

The invention relates to the technical field of organic compound synthesis, in particular to a preparation method of aryl C-F bond functionalization. The invention adopts the photocatalyst, the reaction process is safe and controllable, and the operation in the preparation production process is simplified; the purple LED is used as a reaction energy source, so that the environment is protected, the energy utilization rate is high, and the conversion from light energy to chemical energy can be efficiently realized; the reaction efficiently and greenly produces a very wide range of target products by using simple nucleophiles to attack free radical cationic species generated under visible light catalysis. The invention simplifies the operation steps and shortens the reaction route; and the forward reaction rate is high, and the production efficiency is obviously improved.

Description

Aryl C-F bond functionalization preparation method
Technical Field
The invention relates to the technical field of organic compound synthesis, in particular to a preparation method of aryl C-F bond functionalization.
Background
The fluorine-containing organic compound is widely applied to the fields of medicine, biochemistry, catalysis, material science and the like. In view of the increasing importance of C-F bond formation, C-F bond functionalization is also of great interest, and it is desired to synthesize organic small molecules with novel and diverse structures by functionalizing the C-F bond of fluorine-containing compounds. The bond energy of the inert C-F bond is very high and difficult to activate, so that the carbon-fluorine bond can be modified in the last step of the drug synthesis by utilizing the characteristic, thereby synthesizing the target compound required by people. Since 1973, the Kumada group reported that nickel-catalyzed cross-coupling reactions of aromatic fluorides with Kumada-Corriu were followed by more and more organolithium or organomagnesium reactions with aryl-, alkenyl-, or alkyl-halohydrocarbons under nickel and palladium catalysis. However, these methods still have some disadvantages, such as: 1) the compatibility with functional groups in the Kumada coupling reaction is poor. The strong basicity and nucleophilicity of the grignard reagent may react with many functional groups and thus is not suitable for halogenated hydrocarbons that are unstable in the presence of the grignard reagent. 2) The price of the palladium catalyst is expensive, the amount of the palladium catalyst is a precondition for realizing industrial production, and a recyclable palladium catalyst 3) some metal complexes are sensitive to water and air, which not only complicates the operation, but also causes a safety problem. In addition, in the pharmaceutical and material industries, some tedious processes and special equipment are often required to solve the "transition metal residue problem", and additional resources are consumed to reduce the metal content to a certain level.
How to efficiently and environmentally break, activate and functionalize the carbon-fluorine bonds of different fluorine-containing compounds is a very important research subject of fluorine chemistry, organic synthesis and organometallic chemistry. Therefore, there is a need for a new method to overcome the deficiencies of the prior art, particularly those described above. In recent years, the development of the visible light catalytic chemistry field is changing day by day, and a new path is provided for the construction of aryl C-F bond functionalization.
Disclosure of Invention
The invention aims to overcome the problems in the prior art and provides a preparation method of aryl C-F bond functionalization, so as to overcome the technical problems of limited application range, harsh preparation conditions, low yield, complex process, environmental friendliness and the like of the existing method.
The purpose of the invention is realized by the following technical scheme:
a method for preparing aryl C-F bond functionalization comprises the following steps: reacting a fluorobenzene compound with a nucleophilic reagent under the action of a composite catalyst, wherein the composite catalyst is formed by mixing a visible light catalyst and a metal catalyst;
the visible light catalyst comprises one or more of the following structural formulas of formula (I), (II) and (III):
Figure BDA0003137949460000021
wherein R is6、R7、R8、R9、R10、R11、R12、R13、R14、R15Are identical or different C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkenyl radical, C2-C20Heteroalkenyl, C1-C20Perfluoroalkyl radical, C3-C20Cycloalkenyl radical, C3-C20Heterocycloalkenyl, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl radical、C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl (C)1-C20) Alkyl, heteroaryl (C)1-C20) Alkyl radical, C2-C20Alkenyl (C)1-C20) Alkyl radical, C2-C20Alkynyl (C)1-C20) Alkyl, cyano (C)1-C20) Alkyl, alkyloxycarbonylalkyl; z is an anion; a is a nitrogen atom or a carbon atom.
Preferably, the metal catalyst is Cu2+Or Cu+A complex with ligand (I) or ligand (II), wherein the structures of ligand (I) and ligand (II) are:
Figure BDA0003137949460000031
preferably, the nucleophiles comprise: one or more of allyl trimethylsilane, vinyl ethyl ether, 3-methyl-2, 4-pentanedione, and acetic anhydride.
Preferably, the molar ratio of the visible-light-driven photocatalyst, the metal catalyst and the fluorobenzene compound is (0.05-5): (0.2-20): 1-100).
Preferably, the anion Z is a boron tetrafluoride anion, a chloride ion, an iodide ion, a perchlorate ion or a hexafluorophosphate ion.
Preferably, the reaction takes one or more of acetonitrile, diethyl ether, tetrahydrofuran and dichloromethane as a solvent.
Preferably, the visible light catalyst, the metal catalyst and the fluorobenzene compound are mixed to react at the temperature of 25-80 ℃ by taking the purple LED as a reaction energy source
Preferably, the structural formula of the fluorobenzene compound is as follows:
Figure BDA0003137949460000032
wherein R is1、R2、R3、R4And R5Are identical or different C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkenyl radical, C2-C20Heteroalkenyl, C3-C20Cycloalkenyl radical, C3-C20Heterocycloalkenyl, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl (C)1-C20) Alkyl, heteroaryl (C)1-C20) Alkyl radical, C2-C20Alkenyl (C)1-C20) Alkyl radical, C2-C20Alkynyl (C)1-C20) Alkyl, cyano (C)1-C20) Any one of alkyl, alkyloxycarbonylalkyl, halogen, and hydrogen atom substituent.
The aryl C-F bond functionalized compound prepared by the aryl C-F bond functionalized preparation method.
The application of the aryl C-F bond functionalized compound in the preparation of a drug intermediate.
The bond energy of the inert C-F bond is very high and difficult to activate, and the carbon-fluorine bond can be modified in the last step of the drug synthesis by utilizing the characteristic, so that the target compound required by people can be synthesized. Therefore, the method can be widely used for synthesizing pharmaceutical intermediates and preparing functional materials, thereby enhancing the application of the pharmaceutical intermediates in the pharmaceutical field.
Compared with the prior art, the invention has the following technical effects:
1. the photocatalyst is adopted, the reaction process is safe and controllable, and the operation in the preparation production process is simplified;
2. the purple LED is used as a reaction energy source, so that the environment is protected, the energy utilization rate is high, and the conversion from light energy to chemical energy can be efficiently realized;
3. the reaction efficiently and greenly produces a very wide range of target products by using simple nucleophiles to attack free radical cationic species generated under visible light catalysis.
4. The reactants are selected from simple and commercially available nucleophilic reagents as reactants and commercially available catalysts, the raw materials are low in price and very easy to obtain, and the reactants before reaction can be directly used for preparation production without additional modification protection, so that the operation steps are simplified, and the reaction route is shortened; the forward reaction rate is high, and the production efficiency is obviously improved;
5. the method has the advantages of simple process, low requirement on reaction conditions, safe and controllable reaction process, high atom utilization rate and production efficiency and low environmental pollution pressure, thereby remarkably reducing the production cost and greatly expanding the designability and application prospect of the compounds.
The aryl C-F bond functionalized compound has a typical high-functionalization structure and the advancement of the preparation method, so the aryl C-F bond functionalized compound can be widely used for synthesis of drug intermediates and preparation of functional materials, can effectively reduce the economic cost for preparation of the drug intermediates and the functional materials, and provides the environment-friendly property.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the technical solutions of the present invention will be described in detail below with reference to specific examples and comparative examples. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the examples given herein without any inventive step, are within the scope of the present invention.
The compounds and derivatives thereof referred to in the examples of the present invention are named according to the IUPAC (International Union of pure and applied chemistry) or CAS (chemical abstracts service, Columbus, Ohio) naming system. Accordingly, the groups of compounds specifically referred to in the examples of the present invention are illustrated and described as follows:
with respect to "hydrocarbon group," the minimum and maximum values of the carbon atom content in a hydrocarbon group are indicated by a prefix, e.g., the prefix (Ca-Cb) alkyl indicates any alkyl group containing from "a" to "b" carbon atoms. Thus, for example, (C1-C6) alkyl refers to alkyl groups containing one to six carbon atoms.
"alkoxy" refers to a straight or branched, monovalent, saturated aliphatic chain bonded to an oxygen atom and includes, but is not limited to, groups such as methoxy, ethoxy, propoxy, butoxy, isobutoxy, t-butoxy, and the like. (Ca-Cb) alkoxy means any straight or branched, monovalent, saturated aliphatic chain having an alkyl group containing from "a" to "b" carbon atoms bonded to an oxygen atom.
"alkyl" refers to a straight or branched, monovalent, saturated aliphatic chain including, but not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl, and the like.
"heteroalkyl" means a straight or branched, monovalent, saturated aliphatic chain attached to at least one heteroatom, such as, but not limited to, methylaminoethyl or other similar groups.
"alkenyl" refers to straight or branched chain hydrocarbons having one or more double bonds, including but not limited to, groups such as ethenyl, propenyl, and the like.
"Heteroalkenyl" means a straight or branched chain hydrocarbon with one or more double bonds attached to at least one heteroatom, including but not limited to, for example, vinylaminoethyl or other similar groups.
"alkynyl" refers to a straight or branched chain hydrocarbon with one or more triple bonds, including but not limited to, for example, ethynyl, propynyl, and the like.
"Heteroalkynyl" means a straight or branched chain hydrocarbon with one or more triple bonds attached to at least one heteroatom, including but not limited to, groups such as ethynyl, propynyl, and the like.
"aryl" refers to a cyclic aromatic hydrocarbon including, but not limited to, phenyl, naphthyl, anthryl, phenanthryl, and the like.
"heteroaryl" refers to a monocyclic or polycyclic or fused ring aromatic hydrocarbon in which one or more carbon atoms have been replaced with a heteroatom such as nitrogen, oxygen, or sulfur. If the heteroaryl group contains more than one heteroatom, these heteroatoms may be the same or different. Heteroaryl groups include, but are not limited to, groups such as benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzopyranyl, furanyl, imidazolyl, indazolyl, indolizinyl, indolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, oxazinyl, oxazolyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridine [3,4-b ] indolyl, pyridyl, pyrimidinyl, pyrrolyl, quinolizinyl, quinolyl, quinoxalinyl, thiadiazolyl, thiatriazolyl, thiazolyl, thienyl, triazinyl, triazolyl, xanthenyl, and the like.
"cycloalkyl" refers to a saturated monocyclic or polycyclic alkyl group, possibly fused to an aromatic hydrocarbon group. Cycloalkyl groups include, but are not limited to, groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indanyl, tetrahydronaphthyl, and the like.
"Heterocycloalkyl" means a saturated monocyclic or polycyclic alkyl group, possibly fused to an aromatic hydrocarbon group, in which at least one carbon atom has been replaced by a heteroatom such as nitrogen, oxygen or sulfur. If the heterocycloalkyl group contains more than one heteroatom, these heteroatoms may be the same or different. Heterocycloalkyl groups include, but are not limited to, groups such as azepanyl, azetidinyl, indolinyl, morpholinyl, pyrazinyl, piperidinyl, pyrrolidinyl, tetrahydrofuryl, tetrahydroquinolinyl, tetrahydroindazolyl, tetrahydroindolyl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydroquinoxalinyl, tetrahydrothiopyranyl, thiazolidinyl, thiomorpholinyl, thioxanthyl, and the like.
"cycloalkenyl" refers to an unsaturated, monocyclic or polycyclic alkenyl group with one or more double bonds, possibly fused to an aromatic hydrocarbon group, including, but not limited to, cyclic ethenyl, cyclopropenyl, or other similar groups.
"Heterocycloalkenyl" means an unsaturated, monocyclic or polycyclic alkenyl radical having one or more double bonds, possibly condensed with an aromatic hydrocarbon radical, in which at least one carbon atom is replaced by a heteroatom such as nitrogen, oxygen or sulfur. If the heterocycloalkyl group contains more than one heteroatom, these heteroatoms may be the same or different.
"cycloalkynyl" refers to an unsaturated, monocyclic or polycyclic alkynyl group having one or more triple bonds, possibly fused to an aromatic hydrocarbon group, including, but not limited to, cycloalkynyl, cyclopropynyl, or the like.
"Heterocycloalkynyl" means an unsaturated, monocyclic or polycyclic alkynyl radical having one or more triple bonds, possibly condensed with an aromatic hydrocarbon radical, in which at least one carbon atom has been replaced by a heteroatom such as nitrogen, oxygen or sulfur. If the heterocycloalkyl group contains more than one heteroatom, these heteroatoms may be the same or different.
Example 1
This example provides a method for producing phenylacetaldehyde. The structural formula of phenylacetaldehyde is shown as the following molecular structural formula I1:
Figure BDA0003137949460000071
the preparation method comprises the following steps:
a dry 4mL test tube was charged with mesitylene-substituted acridinium salt photocatalyst (0.05eq), CuCl2(0.2eq), bipyridine (0.2eq) and 0.5mL of anhydrous acetonitrile, 0.2mmol of acetic anhydride (1eq) and 0.2mmol of fluorobenzene were added, argon gas was substituted three times, and reaction time was 24 hours under 390nm Kessil lamp irradiation. After the reaction is finished, the filtrate is dried by spinning, and the target product is obtained by column chromatography separation, wherein the yield is 71 percent.
The result of the correlation characterization analysis is as follows:1H NMR(400MHz；CDCl3)δ＝9.70(1H,t,J＝2Hz),7.30–7.10(5H,m),3.60(2H,d,J＝2Hz)；13C NMR(100MHz；CDCl3)＝199.9,132.3,130.0,129.9,129.4,129.3,127.8,51.0；MS(EI)m/z 120(M) +; HRMS (ES) calculated for C8H8O (M) +120.0570, found 120.0568(M) +. this result further confirms the molecular structure of the product as described above for molecular structure I1.
Example 2
This example provides a process for the preparation of 1-allyl-4-methylbenzene. The structural formula of the 1-allyl-4-methylbenzene is shown as the following molecular structural formula I2:
Figure BDA0003137949460000072
the preparation method refers to the preparation method of phenylacetaldehyde in example 1, and is characterized in that p-methylfluorobenzene (0.2mmol) is adopted to replace fluorobenzene, allyl trimethylsilane (1eq) 0.2mmol is adopted to replace acetic anhydride (1eq) 0.2mmol, filtrate is dried by spinning, and column chromatography separation is carried out to obtain a target product, wherein the yield is 77%. The product I2 prepared was subjected to characterization data analysis, which resulted in:1H NMR(CDCl3,300MHz)δ7.10(s,4H),6.03-5.89(m,1H),5.11-5.03(m,2H),3.35(d,2H,J＝6.6),2.32(s,3H)ppm；13C NMR(CDCl3,75MHz)δ137.7,136.9,135.5,129.1,128.4,115.5,39.8,21.0ppm；IR 2920,2849,1658,1632,1469cm-1；MS calculated for C10H12(m/z)(％):132(59)[M+]this result further confirmed the molecular structure of the product as described above for molecular structure I2 (117).
Example 3
This example provides a process for the preparation of 1-allyl-3-methylbenzene. The structural formula of the 1-allyl-3-methylbenzene is shown as the following molecular structural formula I3:
Figure BDA0003137949460000081
the preparation method refers to the preparation method of phenylacetaldehyde in example 1, and is characterized in that m-methylfluorobenzene (0.2mmol) is adopted to replace fluorobenzene, 0.2mmol of allyltrimethylsilane (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), the filtrate is dried by spinning, and column chromatography separation is carried out to obtain the target product, wherein the yield is 58%. The product I3 prepared was subjected to characterization data analysis, which resulted in:1H NMR(CDCl3,300MHz)δ7.26-7.17(m,1H),7.04-3.99(m,3H),6.04-5.90(m,1H),5.12-5.05(m,2H)3.35(d,2H,J＝6.6),2.33(s,3H)ppm；13CNMR(CDCl3,75MHz)δ140.0,138.0,137.6,129.3,128.3,126.8,125.6,115.6,40.2,21.4ppm；IR 2953,2923,2854,1459,1376,1027cm-1；MS calculated for C10H12:(m/z)(％):132(62)[M+]this result further confirmed the molecular structure of the product as described above for molecular structure I3 (117).
Example 4
This example provides a process for the preparation of 1-allyl-2-methylbenzene. The structural formula of the 1-allyl-2-methylbenzene is shown as the following molecular structural formula I4:
Figure BDA0003137949460000082
the preparation method refers to the preparation method of phenylacetaldehyde in example 1, and is characterized in that o-methylfluorobenzene (0.2mmol) is adopted to replace fluorobenzene, 0.2mmol of allyltrimethylsilane (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), the filtrate is dried by spinning, and column chromatography separation is carried out to obtain the target product, wherein the yield is 50%. The product I4 prepared was subjected to characterization data analysis, which resulted in:1H NMR(CDCl3,300MHz)δ7.14(s,4H),6.02-5.89(m,1H),5.08-4.96(m,2H)3.36(d,2H,J＝6.6),2.28(s,3H)ppm；13C NMR(CDCl3,75MHz)δ138.1,136.6,136.3,130.1,129.1,126.2,126.0,115.6,37.7,19.3ppm；IR 2953,2924,2855,1458cm-1；MS calculated for C10H12:(m/z)(％):132(56)[M+]this result further confirmed the molecular structure of the product as described above for molecular structure I4 (117).
Example 5
This example provides a method for preparing 2-allyl-1, 3, 5-trimethylbenzene. The structural formula of the 2-allyl-1, 3, 5-trimethylbenzene is shown as the following molecular structural formula I5:
Figure BDA0003137949460000091
the preparation method refers to the preparation method of the phenylacetaldehyde in the embodiment 1, and is characterized in that 1, 3, 5-trimethylfluorobenzene (0.2mmol) is adopted to replace fluorobenzene, 0.2mmol of allyltrimethylsilane (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), the filtrate is dried by spinning, and the column chromatography separation is carried out to obtain the target product, wherein the yield is 75%.
The product I5 prepared was subjected to characterization data analysis, which resulted in:1H NMR(CDCl3,300MHz)δ6.85(s,2H),5.95-5.82(m,1H),5.00-4.82(m,2H)3.37-3.34(m,2H),2.25(s,9H)ppm；13C NMR(CDCl3,75MHz)δ136.5,135.5,135.3,133.0,128.7,126.9,33.3,20.8,19.7ppm；IR 2921,2851,1639,1443,1260cm-1；MS calculated for C12H16:(m/z)(％):160(51)[M+]this result further confirmed the molecular structure of the product as described above for molecular structure I5.
Example 6
This example provides 4-allylbiphenyl and a method of making the same. The structural formula of the 4-allyl biphenyl is shown as the following molecular structural formula I6:
Figure BDA0003137949460000092
the preparation method refers to the preparation method of phenylacetaldehyde in example 1, and is characterized in that 4-fluorobiphenyl (0.2mmol) is adopted to replace fluorobenzene, 0.2mmol of allyltrimethylsilane (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), the filtrate is dried by spinning, and column chromatography separation is carried out, so that the target product is obtained, and the yield is 52%.
The product I6 prepared was subjected to characterization data analysis, which resulted in:1H NMR(CDCl3,200MHz)δ7.60-7.24(m,9H),6.10-5.90(m,1H),6.02-5.89(m,1H)5.17-5.06(m,2H),3.42(d,2H,J＝7.0)ppm；13C NMR(CDCl3,50MHz)δ141.1,139.2,139.1,137.4,129.0,128.8,127.2,127.1,116.0,39.8ppm；IR 3057,1638,1486cm-1；MS calculated for C15H14:(m/z)(％):194(100)[M+]this result further confirmed the molecular structure of the product as described above for molecular structure I6.
Example 7
This example provides a process for the preparation of 1-allyl-4-chlorobenzene. The structural formula of the 1-allyl-4-chlorobenzene is shown as the following molecular structural formula I7:
Figure BDA0003137949460000101
the preparation method refers to the preparation method of phenylacetaldehyde in example 1, and is characterized in that 4-chlorofluorobenzene (0.2mmol) is adopted to replace fluorobenzene, 0.2mmol of allyltrimethylsilane (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), the filtrate is dried by spinning, and column chromatography separation is carried out to obtain a target product, wherein the yield is 63%.
The product I7 prepared was subjected to characterization data analysis, which resulted in:1H NMR(CDCl3,300MHz)δ7.24(d,1H,J＝8.4),7.09(d,1H,J＝8.4),5.98-5.85(m,1H),5.09-5.03(m,2H),3.32(d,2H,J＝6.6)ppm；13C NMR(CDCl3,75MHz)δ138.4,136.8,131.8,129.9,128.4,116.2,39.4ppm；IR 2954,2924,2855,1456,1377,1091cm-1；MS calculated for C9H9Cl:(m/z)(％):152(50)[M+]this result further confirmed the molecular structure of the product as described above for molecular structure I7 (117).
Example 8
This example provides a method for preparing 1-allyl-4-bromobenzene. The structural formula of the 1-allyl-4-bromobenzene is shown as the following molecular structural formula I8:
Figure BDA0003137949460000102
the preparation method refers to the preparation method of phenylacetaldehyde in example 1, and is characterized in that 4-bromofluorobenzene (0.2mmol) is adopted to replace fluorobenzene, 0.2mmol of allyltrimethylsilane (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), the filtrate is dried by spinning, and column chromatography separation is carried out, so that the target product is obtained, and the yield is 67%. The product I8 prepared was subjected to characterization data analysis, which resulted in:1H NMR(CDCl3,300MHz)δ7.42(d,1H,J＝8.4),7.07(d,1H,J＝8.4),6.02-5.87(m,1H),5.14-5.05(m,2H),3.34(d,2H,J＝6.9)ppm；13C NMR(CDCl3,75MHz)δ138.9,136.7,131.4,130.3,119.8,116.2,39.5ppm；IR 2953,2924,2853,1488,1460,1024cm-1；MS calculated for C9H9Br:(m/z)(％):196(56)[M+]this result further confirmed the molecular structure of the product as described above for molecular structure I8 (117).
Example 9
This example provides a process for the preparation of 1-allylnaphthalene. The structural formula of the 1-allyl naphthalene is shown as the following molecular structural formula I9:
Figure BDA0003137949460000111
the preparation method refers to the preparation method of the phenylacetaldehyde in the embodiment 1, and is characterized in that 2-fluoronaphthalene (0.2mmol) is adopted to replace fluorobenzene, 0.2mmol of allyltrimethylsilane (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), the filtrate is dried by spinning, and the column chromatography separation is carried out, so that the target product is obtained, and the yield is 72%. The product I9 prepared was subjected to characterization data analysis, which resulted in:1H NMR(CDCl3,300MHz)δ8.00(d,2H,J＝9.0),7.83-7.80(m,1H),7.70(d,1H,J＝8.1),7.47-7.43(m,2H),7.37(d,2H,J＝8.1),7.31(d,2H,J＝7.2),6.16-6.02(m,1H),5.11-5.04(m,2H),3.80(d,2H,J＝6.3)ppm；13C NMR(CDCl3,75MHz)δ136.9,136.0,131.9,128.6,127.8,126.9,126.2,125.8,125.5,124.0,116.1,37.2ppm；IR 2976,1638,1597,1510,1396,993,913cm-1；MS calculated for C13H12:(m/z)(％):168(100)[M+]this result further confirmed the molecular structure of the product as described above for molecular structure I9 (153 (87)).
Example 10
This example provides a method for preparing 1-phenyl-2-propanone. The structural formula of the 1-phenyl-2-acetone is shown as the following molecular structural formula I10:
Figure BDA0003137949460000112
the preparation method refers to the preparation method of the phenylacetaldehyde in the example 1, and is characterized in that 0.2mmol of 3-methyl-2, 4-pentanedione (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), the filtrate is dried by spinning, and column chromatography separation is carried out, so that the target product is obtained, and the yield is 40%.
The product I10 prepared was subjected to characterization data analysis, which resulted in:1H NMR(600MHz,CDCl3):δ7.33-7.30(t,J＝7.5Hz,2H),7.26-7.24(t,J＝7.2Hz,1H),7.20-7.18(d,J＝7.8Hz,2H),3.67(s,2H),2.13(s,3H)；13C NMR(150MHz,CDCl3):δ206.21,134.09,129.31,129.14,128.64,128.47,126.96,126.77,50.80,29.09.MS calculated for C9H10134.18 in% (m/z), and the results confirmed that the molecular structure of the product was the same as that of the above-mentioned molecular structure I10.
Example 11
This example provides a method for preparing p-methoxyphenylacetone. The structural formula of the p-methoxy phenyl acetone is shown as the following molecular structural formula I11:
Figure BDA0003137949460000121
the preparation method refers to the preparation method of the phenylacetaldehyde in the embodiment 1, and is characterized in that 0.2mmol of 3-methyl-2, 4-pentanedione (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), 0.2mmol of p-anisole is adopted to replace fluorobenzene, the filtrate is dried by spinning, and the column chromatography separation is carried out to obtain the target product with the yield of 72%.
The product I11 prepared was subjected to characterization data analysis, which resulted in:1H NMR(600MHz,CDCl3):δ7.11-7.10(d,J＝8.4Hz,2H),6.87-6.85(d,J＝8.4Hz,2H),3.77(s,3H),3.61(s,2H),2.12(s,3H)；13C NMR(150MHz,CDCl3):δ206.67,158.46,130.30,130.14,126.10,114.02,113.91,55.10,49.86,28.92.HRMS(ESI/[M+H+])calcd.for C10H13O2165.0910.Found:165.0904. the results further confirm that the molecular structure of the product is as described above for molecular structure I11.
Example 12
This example provides a process for the preparation of p-trifluoromethylphenylacetone. The structural formula of the p-trifluoromethylphenyl acetone is shown as the following molecular structural formula I12:
Figure BDA0003137949460000122
the preparation method refers to the preparation method of the phenylacetaldehyde in the embodiment 1, and is characterized in that 0.2mmol of 3-methyl-2, 4-pentanedione (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), 0.2mmol of p-fluorotrifluorotoluene is adopted to replace fluorobenzene, the filtrate is dried by spinning, and the column chromatography separation is carried out to obtain the target product with the yield of 57%. The product I12 prepared was subjected to characterization data analysis, which resulted in:1H NMR(600MHz,CDCl3):δ7.60-7.59(d,J＝7.8Hz,2H),7.32-7.31(d,J＝7.8Hz,2H),3.78(s,2H),2.20(s,3H)；13C NMR(150MHz,CDCl3):δ205.13,138.00,129.87,129.71,129.46,129.25,125.61,125.49,124.97,123.17,50.32,29.61.HRMS(ESI/[M+H+])calcd.for C10H10F3o203.0678 Found 203.0683 the results further confirm that the molecular structure of the product is as described above for molecular structure I12.
Example 13
This example provides a method for preparing 4-methyl propiophenone. The structural formula of the 4-methyl propiophenone is shown as the following molecular structural formula I13:
Figure BDA0003137949460000131
the preparation method refers to the preparation method of the phenylacetaldehyde in the embodiment 1, and is characterized in that 0.2mmol of 3-methyl-2, 4-pentanedione (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), 0.2mmol of p-fluorotoluene is adopted to replace fluorobenzene, the filtrate is dried by spinning, and the column chromatography separation is carried out to obtain the target product with the yield of 61%.
The product I13 prepared was subjected to characterization data analysis, which resulted in:1H NMR(600MHz,CDCl3):δ7.14-7.13(d,J＝7.8Hz,2H),7.09-7.07(d,J＝8.4Hz,2H),3.64(s,2H),2.32(s,3H),2.12(s,3H)；13C NMR(150MHz,CDCl3):δ206.68,136.63,131.16,129.51,129.32,129.20,129.14,50.60,29.15,21.09.HRMS calcd.for C10H12o. 148.2.Found:148.2. this result further confirms the molecular structure of the product as in the above molecular structure I13.
Example 14
This example provides a method for preparing 3-methyl propiophenone. The structural formula of the 3-methyl propiophenone is shown as the following molecular structural formula I14:
Figure BDA0003137949460000132
the preparation method refers to the preparation method of the phenylacetaldehyde in the embodiment 1, and is characterized in that 0.2mmol of 3-methyl-2, 4-pentanedione (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), 0.2mmol of 3-fluorotoluene is adopted to replace fluorobenzene, the filtrate is dried by spinning, and the column chromatography separation is carried out to obtain the target product with the yield of 57%.
The product I14 prepared was subjected to characterization data analysis, which resulted in:1H NMR(600MHz,CDCl3):δ7.25-7.21(q,J＝8.8Hz,1H),7.09-7.07(d,J＝7.2Hz,1H),7.02-6.99(t,J＝6.6Hz,2H),3.65(s,2H),2.34(s,3H)2.14(s,3H)；13C NMR(150MHz,CDCl3):δ206.57,138.33,134.05,130.11,129.96,128.64,128.49,127.81,127.66,126.39,126.24,50.93,29.17,21.32.HRMS calcd.for C10H12o. 148.2.Found:148.2. this result further confirms the molecular structure of the product as in the above molecular structure I14.
Example 15
This example provides a process for the preparation of 4-isopropylphenylacetone. The structural formula of the 4-isopropyl phenylacetone is shown as the following molecular structural formula I15:
Figure BDA0003137949460000141
the preparation method refers to the preparation method of the phenylacetaldehyde in the embodiment 1, and is characterized in that 0.2mmol of 3-methyl-2, 4-pentanedione (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), 0.2mmol of 4-fluoroisopropylbenzene is adopted to replace fluorobenzene, the filtrate is dried by spinning, and the column chromatography separation is carried out to obtain the target product with the yield of 50%. The product I15 prepared was subjected to characterization data analysis, which resulted in:1H NMR(300MHz,CDCl3):δ7.12-7.03(m,4H),3.57(s,2H),2.85-2.76(m,1H),2.06(s,3H),1.17(s,3H),1.15(s,3H)；13C NMR(75MHz,CDCl3):δ207.04,147.86,131.70,129.52,127.05,50.85,33.96,29.50,24.20.HRMS calcd.for C12H16o. 176.25.Found:176.25. this result further confirmed the molecular structure of the product as described above for molecular structure I15.
Example 16
This example provides a method for preparing 4-chlorophenyl propanone. The structural formula of the 4-chlorophenylacetone is shown as the following molecular structural formula I16:
Figure BDA0003137949460000142
the preparation method refers to the preparation method of the phenylacetaldehyde in the embodiment 1, and is characterized in that 0.2mmol of 3-methyl-2, 4-pentanedione (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), 0.2mmol of 4-fluorobenzene is adopted to replace fluorobenzene, the filtrate is dried by spinning, and the column chromatography separation is carried out to obtain the target product with the yield of 51%.
The product I16 prepared was subjected to characterization data analysis, which resulted in:1H NMR(600MHz,CDCl3):δ7.30-7.29(d,J＝7.8Hz,2H),7.13-7.12(d,J＝7.8Hz,2H),3.67(s,2H),2.16(s,3H)；13C NMR(150MHz,CDCl3):δ205.59,132.89,132.49,130.76,130.61,128.81,128.66,49.93,29.34.HRMS calcd.for C9H9ClO:168.62.Found:168.62. the results further confirm that the molecular structure of the product is as described above for molecular structure I16.
Example 17
This example provides a method for preparing 4-nitrophenylacetone. The structural formula of the 7-methoxy-1- (3-chloro-phenyl) -fluorobenzene is shown as the following molecular structural formula I17:
Figure BDA0003137949460000151
the preparation method refers to the preparation method of the phenylacetaldehyde in the embodiment 1, and is characterized in that 0.2mmol of 3-methyl-2, 4-pentanedione (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), 0.2mmol of 4-fluoronitrobenzene is adopted to replace fluorobenzene, the filtrate is dried by spinning, and the column chromatography separation is carried out to obtain the target product with the yield of 48%. The product I17 prepared was subjected to characterization data analysis, which resulted in: 1H NMR (400 MH)z,CDCl3):δ8.21-8.19(d,J＝8.4Hz,2H),7.38-7.36(d,J＝8.8Hz,2H),3.87(s,2H),2.25(s,3H)；13C NMR(100MHz,CDCl3):δ204.40,141.38,130.42,123.69,115.57,49.96,29.81.HRMS calcd.for C9H9NO3179.17 Found 179.17 the results further confirm that the molecular structure of the product is as described above for molecular structure I17.
Example 18
This example provides a method for preparing 4- (2-oxopropyl) benzoic acid. The structural formula of the 4- (2-oxopropyl) benzoic acid is shown as the following molecular structural formula I18:
Figure BDA0003137949460000152
the preparation method refers to the preparation method of the phenylacetaldehyde in the embodiment 1, and is characterized in that 0.2mmol of 3-methyl-2, 4-pentanedione (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), 0.2mmol of 4-fluorobenzoic acid is adopted to replace fluorobenzene, the filtrate is dried by spinning, and the column chromatography separation is carried out to obtain the target product, wherein the yield is 41%. The product I18 prepared was subjected to characterization data analysis, which resulted in:1H NMR(400MHz,d6-DMSO):δ7.86-7.84(d,J＝8.0Hz,2H),7.26-7.24(d,J＝8.0Hz,2H),3.81(s,2H),2.10(s,3H)；13C NMR(100MHz,d6-DMSO):δ205.85,167.74,140.55,130.37,129.75,129.55,49.82,30.13.HRMS calcd.for C10H10O3178.18 Found 178.18 the results further confirm that the molecular structure of the product is as described above under I18.
Example 19
This example provides a method for preparing 4-biphenylacetone. The structural formula of the 4-biphenylacetone is shown as the following molecular structural formula I19:
Figure BDA0003137949460000161
the preparation method refers to the preparation method of the phenylacetaldehyde in the embodiment 1, and is characterized in that 0.2mmol of 3-methyl-2, 4-pentanedione (1eq) is adopted to replace 0.2mmol of acetic anhydride (1eq), 0.2mmol of 4-fluorobiphenyl is adopted to replace fluorobenzene, the filtrate is dried by spinning, and the column chromatography separation is carried out to obtain the target product, wherein the yield is 57%.
The product I19 prepared was subjected to characterization data analysis, which resulted in:1H NMR(600MHz,CDCl3):δ7.58-7.55(q,J＝6.2Hz,4H),7.43-7.41(t,J＝7.8Hz,2H),7.34-7.32(t,J＝7.2Hz,1H),7.26-7.25(d,J＝7.8Hz,2H),3.72(s,2H),2.17(s,3H)；13C NMR(150MHz,CDCl3):δ206.25,140.59,139.90,133.14,129.82,129.66,128.76,128.61,127.43,127.31,126.99,126.89,126.57,50.48,29.33,29.29.HRMS calcd.for C15H14o210.27107, Found 210.27107, this result further confirmed the molecular structure of the product as described above for molecular structure I19.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the protection scope of the present invention, although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims (10)

1. A method for preparing an aryl C-F bond functionalization is characterized by comprising the following steps: reacting a fluorobenzene compound with a nucleophilic reagent under the action of a composite catalyst, wherein the composite catalyst is formed by mixing a visible light catalyst and a metal catalyst;
the visible light catalyst comprises one or more of the following structural formulas of formula (I), (II) and (III):
Figure FDA0003137949450000011
wherein R is6、R7、R8、R9、R10、R11、R12、R13、R14、R15Are identical or different C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkenyl radical, C2-C20Heteroalkenyl, C1-C20Perfluoroalkyl radical, C3-C20Cycloalkenyl radical, C3-C20Heterocycloalkenyl, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl (C)1-C20) Alkyl, heteroaryl (C)1-C20) Alkyl radical, C2-C20Alkenyl (C)1-C20) Alkyl radical, C2-C20Alkynyl (C)1-C20) Alkyl, cyano (C)1-C20) Alkyl, alkyloxycarbonylalkyl; z is an anion; a is a nitrogen atom or a carbon atom.
2. The method for preparing aryl C-F bond functionalization according to claim 1, wherein the metal catalyst is Cu2+Or Cu+A complex with ligand (I) or ligand (II), wherein the structures of ligand (I) and ligand (II) are:
Figure FDA0003137949450000021
3. the method for preparing aryl C-F bond functionalization according to claim 1, wherein said nucleophile comprises: one or more of allyl trimethylsilane, vinyl ethyl ether, 3-methyl-2, 4-pentanedione, and acetic anhydride.
4. The method for preparing aryl C-F bond functionalization according to claim 1, wherein the molar ratio of the visible light catalyst, the metal catalyst and the fluorobenzene compound is (0.05-5): (0.2-20): 1-100).
5. The method for preparing aryl C-F bond functionalization according to claim 1, wherein the anion Z is boron tetrafluoride anion, chloride ion, iodide ion, perchlorate ion or hexafluorophosphate ion.
6. The method for preparing the aryl C-F bond functionalization according to the claim 1, wherein the reaction uses one or more of acetonitrile, diethyl ether, tetrahydrofuran and dichloromethane as a solvent.
7. The aryl C-F bond functionalization preparation method according to claim 1, wherein a visible light catalyst, a metal catalyst and a fluorobenzene compound are mixed to take a purple LED as a reaction energy source, and the reaction is carried out at a temperature of 25-80 ℃.
8. The method for preparing aryl C-F bond functionalization according to claim 1, wherein the structural formula of the fluorobenzene compound is as follows:
Figure FDA0003137949450000022
wherein R is1、R2、R3、R4And R5Are identical or different C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkenyl radical, C2-C20Heteroalkenyl, C3-C20Cycloalkenyl radical, C3-C20Heterocycloalkenyl, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl (C)1-C20) Alkyl, heteroaryl (C)1-C20) Alkyl radical, C2-C20Alkenyl (C)1-C20) Alkyl radical, C2-C20Alkynyl (C)1-C20) Alkyl, cyano (C)1-C20) Any one of alkyl, alkyloxycarbonylalkyl, halogen, and hydrogen atom substituent.
9. An aryl C-F bond functionalized compound prepared by the aryl C-F bond functionalization preparation method of any one of claims 1 to 8.
10. Use of an aryl C-F bond functionalised compound according to claim 9 in the manufacture of a pharmaceutical intermediate.
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CN103951694A (en) * 2014-04-14 2014-07-30 上海大学 Acridine or benzacridine derivative and synthesis method thereof
CN104151243A (en) * 2014-07-22 2014-11-19 清华大学 Method for preparing multi-substituted acridine derivative with high efficiency
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CN103951694A (en) * 2014-04-14 2014-07-30 上海大学 Acridine or benzacridine derivative and synthesis method thereof
CN104151243A (en) * 2014-07-22 2014-11-19 清华大学 Method for preparing multi-substituted acridine derivative with high efficiency
CN112125840A (en) * 2020-08-11 2020-12-25 河南师范大学 Based on CO2Method for preparing diaryl ether compound by participated C-F bond activation

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