Method for generating and capturing alkyl free radicals, products thereof and applications of the products

Abstract

The present application provides a method for generating and capturing alkyl free radicals, and its products and applications of the products, the method comprising the following steps: subjecting primary alkyl ethylbenzene and a capturing agent to a light catalytic reaction under photocatalytic conditions; the structure of primary alkyl ethylbenzene is as follows: the capturing agent contains an unsaturated bond or an electron-withdrawing group. The method for generating and capturing alkyl free radicals provided in the present application uses primary alkyl ethylbenzene as a reaction substrate, oxidizes alkyl ethylbenzene by single electron transfer, and then induces carbon-carbon bond breakage under photocatalytic conditions to generate alkyl free radicals, and then the alkyl free radicals react with the capturing agent for synthesis, which significantly reduces the production cost of preparing such captured products and greatly expands the designability and application prospects of such compounds.

Description

Technical Field

[0001] The present application belongs to the technical field of organic compound synthesis, and more specifically, to a method for generating and capturing alkyl free radicals, and its products and applications of the products. Background Art

[0002] With the understanding of photocatalytic mechanism and the development of photoredox catalysts, visible light-induced photoredox catalysis has developed rapidly and achieved remarkable achievements, which has completely changed modern free radical chemistry. Among them, alkyl radicals play an indispensable role in the development of new synthetic methods under photo / electrochemical catalysis.

[0003] Typically, precursors of alkyl radicals undergo single electron transfer with the aid of photoredox catalysts to generate transient alkyl radicals that can participate in various bond-forming processes in a chemo- and stereo-selective manner. A large number of alkyl radical precursors have been developed, which basically have heteroatomic groups that can be modified with functional groups to reduce the energy barrier between the substrate and the excited state of the photosensitizer. Despite these advances, the use of common, commercially available chemical raw materials with pure alkyl skeletons to generate alkyl radicals in a precisely controlled manner has received little attention. Direct generation of alkyl radicals from simple, unactivated pure alkyl precursors remains an important challenge in photoredox catalysis due to the high oxidation potential of pure alkyl skeletons. Summary of the invention

[0004] Based on this, an object of the present application is to provide a method for generating and capturing alkyl radicals to solve the technical problem in the prior art that directly generating alkyl radicals from simple unactivated pure alkyl precursors is still an important challenge in photoredox catalysis.

[0005] Another object of the present application is to provide a product prepared by the above method.

[0006] Another object of the present application is to provide applications of the above products.

[0007] To achieve the above purpose, the technical solution adopted in this application is:

[0008] A method for generating and capturing alkyl free radicals comprises the following steps:

[0009] The primary alkylethylbenzene and the capture agent are subjected to a photocatalytic reaction under photocatalytic conditions;

[0010] The structure of primary alkyl ethylbenzene is as follows:

[0011]

[0012] R1 is any one of an alkyl group, a heteroalkyl group, a cycloalkyl group, a heterocycloalkyl group, an alkenyl group, a heteroalkenyl group, a cycloalkenyl group, a heterocycloalkenyl group, an alkynyl group, a heteroalkynyl group, a cycloalkynyl group, a heterocycloalkynyl group, an alkoxy group, an alkenylalkyl group, an alkynylalkyl group, a cyanoalkyl group, an alkyloxycarbonylalkyl group, a silylalkyl group, a halogen group, a phthalimide group, and a hydrogen atom;

[0013] The capture reagent contains an unsaturated bond or an electron-withdrawing group.

[0014] Optionally, the method of subjecting primary alkylethylbenzene and a capture agent to a photocatalytic reaction under photocatalytic conditions comprises the following steps:

[0015] Primary alkylethylbenzene, capture reagent, photocatalyst solution and additives are mixed and subjected to photocatalytic reaction under blue light irradiation.

[0016] Optionally, the capture agent is benzylidenemalononitrile;

[0017] The structure of the product of the photocatalytic reaction is as follows:

[0018]

[0019] Optionally, the photocatalyst is an acridinium salt photocatalyst.

[0020] Optionally, the general structural formula of the acridinium salt catalyst is as follows:

[0021]

[0022] Wherein, X is any one of tetrafluoroborate anion, hexafluorophosphate anion and perchlorate anion;

[0023] Ar is an aryl group or a substituted aryl group;

[0024] R2 and R3 are each independently any one of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkenyl, heteroalkenyl, cycloalkenyl, heterocycloalkenyl, alkynyl, heteroalkynyl, cycloalkynyl, heterocycloalkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, alkenylalkyl, alkynylalkyl, and cyanoalkyl.

[0025] Optionally, the additives include water and an oxidizing agent.

[0026] Optionally, the molar ratio of the photocatalyst, the oxidant, and water is (0.1-20):(0.1-20):(0.2-40);

[0027] And / or, the oxidant includes at least one of persulfate, high-valent iodine, quinones, potassium permanganate, peroxides, oxygen and N-fluorobenzenesulfonimide.

[0028] Optionally, the product of the photocatalytic reaction includes one of the following structural formulas:

[0029]

[0030] And, a product prepared by the above-mentioned method for generating and capturing alkyl radicals.

[0031] And, the application of the above products in the synthesis of drug intermediates, functional materials and metal ligand preparation.

[0032] The beneficial effects provided by this application are:

[0033] 1. The method for generating and capturing alkyl free radicals provided in the present application uses primary alkyl ethylbenzene as a reaction substrate, oxidizes alkyl ethylbenzene by single electron transfer, and then induces the cleavage of the carbon-carbon bond under the condition of a photocatalyst to generate alkyl free radicals, which then undergo a synthesis reaction with a capture agent; the method for generating and capturing alkyl free radicals in the present application significantly reduces the production cost of preparing such captured products, and also greatly expands the designability and application prospects of such compounds;

[0034] 2. The product prepared by the above-mentioned method of generating and capturing alkyl free radicals, the addition product prepared by this method has high functionality, making it more diversified in the application of drug intermediate synthesis, functional materials and metal ligands, and can be widely used in organic synthetic chemistry, biochemistry, asymmetric catalysis, pesticide and pharmaceutical research fields, such as for the synthesis of drug intermediates, preparation of chiral ligands and functional materials, which can effectively reduce the economic cost of the preparation of drug intermediates and functional materials, and the product is environmentally friendly and conducive to application and promotion. DETAILED DESCRIPTION

[0035] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present application more clearly understood, the present application is further described in detail in the following embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0036] The compounds and their derivatives involved in the examples of the present application are named according to the IUPAC (International Union of Pure and Applied Chemistry) or CAS (Chemical Abstracts Service, located in Columbus, Ohio) naming system. Therefore, the compound groups specifically involved in the examples of the present application are described and explained as follows:

[0037] With respect to "hydrocarbon groups", the minimum and maximum carbon atom content of the hydrocarbon group is indicated by a prefix, for example, the prefix (C-C) alkyl represents any alkyl group containing from "a" to "b" carbon atoms. Thus, for example, (C1-C6) alkyl refers to an alkyl group containing from one to six carbon atoms.

[0038] "Alkoxy" refers to a straight or branched, monovalent, saturated aliphatic chain bonded to an oxygen atom, including but not limited to methoxy, ethoxy, propoxy, butoxy, isobutoxy, tert-butoxy and other similar groups. (Ca-Cb) alkoxy refers to any straight or branched, monovalent, saturated aliphatic chain bonded to an oxygen atom in an alkyl group containing "a" to "b" carbon atoms.

[0039] "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 other similar groups.

[0040] "Heteroalkyl" refers to a linear or branched, monovalent, saturated aliphatic chain attached to at least one heteroatom, such as, but not limited to, methylaminoethyl or other similar groups.

[0041] "Alkenyl" refers to straight or branched chain hydrocarbons having one or more double bonds, including but not limited to ethenyl, propenyl, and other similar groups.

[0042] "Heteroalkenyl" refers to a straight or branched hydrocarbon chain with one or more double bonds attached to at least one heteroatom, including but not limited to vinylaminoethyl or other similar groups.

[0043] "Alkynyl" refers to straight or branched chain hydrocarbons having one or more triple bonds, including but not limited to ethynyl, propynyl, and other similar groups.

[0044] "Heteroalkynyl" refers to a straight or branched chain hydrocarbon having one or more triple bonds attached to at least one heteroatom, including but not limited to ethynyl, propynyl and other similar groups.

[0045] "Aryl" refers to a cyclic aromatic hydrocarbon, including but not limited to phenyl, naphthyl, anthracenyl, phenanthrenyl and other similar groups.

[0046] "Heteroaryl" refers to a monocyclic or polycyclic or condensed aromatic hydrocarbon in which one or more carbon atoms have been replaced by heteroatoms such as nitrogen, oxygen or sulfur. If the heteroaryl contains more than one heteroatom, these heteroatoms may be the same or different. Heteroaryl groups include, but are not limited to, benzofuranyl, benzothiophenyl, 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, pyridin[3,4-b]indolyl, pyridyl, pyrimidinyl, pyrrolyl, quinolizinyl, quinolyl, quinoxalinyl, thiadiazolyl, thiatriazolyl, thiazolyl, thienyl, triazinyl, triazolyl, xanthenyl and other similar groups.

[0047] "Cycloalkyl" refers to a saturated monocyclic or polycyclic alkyl group, which may be fused with an aromatic hydrocarbon group. Cycloalkyl includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indanyl, tetrahydronaphthyl and other similar groups.

[0048] "Heterocycloalkyl" refers to a saturated monocyclic or polycyclic alkyl group, which may be 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 includes, but is not limited to, azepanyl, azetidinyl, dihydroindole, morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroindazolyl, tetrahydroindolyl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydroquinoxalinyl, tetrahydrothiopyranyl, thiazolidinyl, thiomorpholinyl, thioxanthenyl, thioxanthyl and other similar groups.

[0049] "Cycloalkenyl" refers to an unsaturated, monocyclic or polycyclic alkenyl group having one or more double bonds, which may be fused to an aromatic hydrocarbon group, including but not limited to cyclovinyl, cyclopropenyl or other similar groups.

[0050] "Heterocycloalkenyl" refers to an unsaturated, monocyclic or polycyclic alkenyl group with one or more double bonds, which may be fused to an aromatic hydrocarbon group, and 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.

[0051] "Cycloalkynyl" refers to an unsaturated, monocyclic or polycyclic alkynyl group having one or more triple bonds, which may be fused to an aromatic hydrocarbon group, including but not limited to cycloethynyl, cyclopropynyl or other similar groups.

[0052] "Heterocycloalkynyl" refers to an unsaturated, monocyclic or polycyclic alkynyl group with one or more triple bonds, which may be fused to an aromatic hydrocarbon group, and 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.

[0053] The present invention provides a method for generating and capturing alkyl radicals, comprising the following steps:

[0054] The primary alkylethylbenzene and the capture agent are subjected to a photocatalytic reaction under photocatalytic conditions;

[0055] The capture reagent contains an unsaturated bond or an electron-withdrawing group.

[0056] The structure of primary alkyl ethylbenzene is as follows:

[0057]

[0058] R1 is any one of an alkyl group, a heteroalkyl group, a cycloalkyl group, a heterocycloalkyl group, an alkenyl group, a heteroalkenyl group, a cycloalkenyl group, a heterocycloalkenyl group, an alkynyl group, a heteroalkynyl group, a cycloalkynyl group, a heterocycloalkynyl group, an alkoxy group, an alkenylalkyl group, an alkynylalkyl group, a cyanoalkyl group, an alkyloxycarbonylalkyl group, a silylalkyl group, a halogen group, a phthalimide group, and a hydrogen atom.

[0059] In primary alkylethylbenzene, the connection between the phenyl group and the methyl group is relatively stable, and the β-carbon bond is relatively weak, so β-breakage occurs to obtain an alkyl free radical containing an R1 group.

[0060] The method for generating and capturing alkyl radicals provided in the embodiment of the present application uses primary alkyl ethylbenzene as a reaction substrate, oxidizes the alkyl ethylbenzene through single electron transfer, and then induces light to break the carbon-carbon bond under photocatalytic conditions to generate alkyl radicals, which are then captured by a capture reagent to undergo a synthesis reaction.

[0061] The reactant primary alkylethylbenzene acts as a nucleophile and can attack compounds containing unsaturated bonds or electron-withdrawing groups, causing an addition reaction between the primary alkylethylbenzene and the capture reagent. This not only effectively improves the atomic utilization of the reactants, but also broadens the limitations of the substrates, thereby efficiently and greenly preparing target products with high chemical selectivity and a wide range.

[0062] The method for generating and capturing alkyl radicals in the embodiments of the present application significantly reduces the production cost of preparing such captured products, and also greatly expands the designability and application prospects of such compounds.

[0063] Optionally, the method of subjecting primary alkylethylbenzene and a capture agent to a photocatalytic reaction under photocatalytic conditions comprises the following steps:

[0064] Primary alkylethylbenzene, capture reagent, photocatalyst solution and additives are mixed and subjected to photocatalytic reaction under blue light irradiation.

[0065] Optionally, the capture agent is benzylidenemalononitrile, the structure of which is as follows:

[0066] There is an unsaturated bond between the benzylidene group and the cyano group, which can react with alkyl radicals to obtain a stable carbon-carbon single bond.

[0067] Then, the product structure of the photocatalytic reaction of primary alkyl ethylbenzene and benzylidene malononitrile is as follows:

[0068]

[0069] R1 is any one of an alkyl group, a heteroalkyl group, a cycloalkyl group, a heterocycloalkyl group, an alkenyl group, a heteroalkenyl group, a cycloalkenyl group, a heterocycloalkenyl group, an alkynyl group, a heteroalkynyl group, a cycloalkynyl group, a heterocycloalkynyl group, an alkoxy group, an alkenylalkyl group, an alkynylalkyl group, a cyanoalkyl group, an alkyloxycarbonylalkyl group, a silylalkyl group, a halogen group, a phthalimide group, and a hydrogen atom.

[0070] Specifically, R1 can be selected from any one of C1-C20 alkyl, C1-C20 heteroalkyl, C3-C20 cycloalkyl, C3-C20 heterocycloalkyl, C2-C20 alkenyl, C2-C20 heteroalkenyl, C3-C20 cycloalkenyl, C3-C20 heterocycloalkenyl, C2-C20 alkynyl, C2-C20 heteroalkynyl, C3-C20 cycloalkynyl, C3-C20 heterocycloalkynyl, C1-C20 alkoxy, C2-C20 alkenyl (C1-C20) alkyl, C2-C20 alkynyl (C1-C20) alkyl, cyano (C1-C20) alkyl, alkyloxycarbonyl alkyl, silyl alkyl C3-C20, halogen, phthalimide, and hydrogen atom.

[0071] When R1 is a C1-C20 alkyl group, the C1-C20 alkyl group may be a (C1-C10) alkyl group, a (C1-C5) alkyl group, a (C1-C4) alkyl group, a (C1-C3) alkyl group or a (C1-C2) alkyl group, etc. In some embodiments, the (C1-C20) alkyl group may be any one of a methyl group, an ethyl group, a propyl group, a butyl group, an isobutyl group, a pentyl group, an isopentyl group, etc.

[0072] When R1 is (C1-C20) heteroalkyl, (C1-C20) heteroalkyl may be (C1-C10) heteroalkyl, (C1-C5) heteroalkyl, (C1-C4) heteroalkyl, (C1-C3) heteroalkyl or (C1-C2) heteroalkyl, etc. In some embodiments, the heteroatom of the heteroalkyl may be a halogen or a nitrogen atom, etc.

[0073] When R1 is (C3-C20)cycloalkyl, the (C3-C20)cycloalkyl may be (C3-C10)cycloalkyl, (C3-C5)cycloalkyl or (C3-C4)cycloalkyl, etc. In one embodiment, the (C3-C20)cycloalkyl may be one of cyclopropyl, cyclobutyl, cyclopentyl, etc.

[0074] When R1 is a (C3-C20)heterocycloalkyl group, the (C3-C20)heterocycloalkyl group may be a (C3-C10)heterocycloalkyl group, a (C3-C10)heterocycloalkyl group, a (C3-C5)heterocycloalkyl group or a (C3-C4)heterocycloalkyl group, etc. In one embodiment, the heteroatom in the heterocycloalkyl group may be a halogen, a nitrogen atom, etc.

[0075] When R1 is (C2-C20)alkenyl, (C2-C20)alkenyl may be (C3-C10)alkenyl, (C3-C5)alkenyl, (C3-C4)alkenyl or (C2-C3)alkenyl, etc. In some embodiments, (C2-C20)alkenyl may specifically be ethenyl, propenyl, butenyl, pentenyl, etc.

[0076] When R1 is (C2-C20) heteroalkenyl, the (C2-C20) heteroalkenyl may be (C2-C10) heteroalkenyl, (C3-C10) heteroalkenyl, (C3-C5) heteroalkenyl, (C3-C4) heteroalkenyl or (C2-C3) heteroalkenyl, etc. In some embodiments, the heteroatom of the heteroalkenyl may be a halogen, a nitrogen atom, a sulfur atom, etc.

[0077] When R is (C3-C20)cycloalkenyl, the (C3-C20)cycloalkenyl may be (C3-C10)cycloalkenyl, (C3-C5)cycloalkenyl, or (C3-C4)cycloalkenyl, etc. In some embodiments, the (C3-C20)cycloalkenyl may be cyclopropenyl, cyclobutenyl, cyclopentenyl, etc.

[0078] When R1 is (C3-C20)heterocycloalkenyl, the (C3-C20)heterocycloalkenyl may be (C3-C10)heterocycloalkenyl, (C3-C5)heterocycloalkenyl or (C3-C4)heterocycloalkenyl, etc. In some embodiments, the heteroatom of the heterocycloalkenyl may be a halogen, a nitrogen atom, a sulfur atom, etc.

[0079] When R1 is (C2-C20)alkynyl, (C2-C20)alkynyl may be (C2-C10)alkynyl, (C3-C10)alkynyl, (C3-C5)alkynyl, (C3-C4)alkynyl or (C2-C3)alkynyl, etc. In some embodiments, (C2-C20)alkynyl may be one of ethynyl, propynyl, butynyl, pentynyl, etc.

[0080] When R1 is a (C2-C20) heteroalkynyl group, the (C2-C20) heteroalkynyl group may be a (C2-C10) heteroalkynyl group, a (C3-C10) heteroalkynyl group, a (C3-C5) heteroalkynyl group, a (C3-C4) heteroalkynyl group or a (C2-C3) heteroalkynyl group, etc. In some embodiments, the heteroatom of the heteroalkynyl group may be a halogen, a nitrogen atom, a sulfur atom, etc.

[0081] When R1 is (C3-C20)cycloalkynyl, the (C3-C20)cycloalkynyl may be (C3-C10)cycloalkynyl, (C3-C5)cycloalkynyl, (C3-C4)cycloalkynyl, etc. In some embodiments, the (C2-C20)cycloalkynyl may be cyclopropynyl, cyclobutynyl, cyclopentynyl, etc.

[0082] When R1 is a (C3-C20)heterocycloalkynyl group, the (C3-C20)heterocycloalkynyl group may be a (C3-C10)heterocycloalkynyl group, a (C3-C5)heterocycloalkynyl group or a (C3-C4)heterocycloalkynyl group, etc. In some embodiments, the heteroatom of the heterocycloalkynyl group may be a halogen, a nitrogen atom, a sulfur atom, etc.

[0083] When R1 is (C1-C20)alkoxy, (C1-C20)alkoxy may be (C1-C10)alkoxy, (C1-C8)alkoxy, (C1-C6)alkoxy, (C1-C4)alkoxy, (C1-C3)alkoxy or (C1-C2)alkoxy, etc. In some embodiments, (C1-C20)alkoxy may be, but is not limited to, methyloxy, ethyloxy, propyloxy, etc.

[0084] When R1 is (C2-C20)alkenyl(C1-C20)alkyl, the (C2-C20)alkenyl(C1-C20)alkyl may be (C2-C10)alkenyl(C1-C10)alkyl or (C2-C5)alkenyl(C1-C3)alkyl, etc. In some embodiments, the (C2-C20)alkenyl(C1-C20)alkyl may be 2-butenyl, 2-pentenyl, 3-hexenyl, 3-heptenyl, etc.

[0085] When R1 is (C2-C20)alkynyl(C1-C20)alkyl, (C2-C20)alkynyl(C1-C20)alkyl may be (C2-C10)alkynyl(C1-C10)alkyl, (C2-C5)alkynyl(C1-C3)alkyl, etc. In some embodiments, the (C2-C20)alkynyl(C1-C20)alkyl may be 2-butynyl, 2-pentynyl, 3-hexynyl, 3-heptynyl, etc.

[0086] When R1 is a cyano (C1-C20) alkyl group, the cyano (C1-C20) alkyl group may be a cyano (C1-C10) alkyl group, a cyano (C1-C5) alkyl group, a cyano (C1-C4) alkyl group, a cyano (C1-C3) alkyl group, a cyano (C1-C2) alkyl group, etc. In some embodiments, the cyano (C1-C20) alkyl group may be a cyanomethyl group, a cyanoethyl group, a cyanopropyl group, a cyanobutyl group, a cyanopentyl group, etc.

[0087] When R1 is an alkyloxycarbonylalkyl, the alkyloxycarbonylalkyl may be (C1-C10)alkyloxycarbonyl(C1-C10)alkyl, (C1-C5)alkyloxycarbonyl(C1-C5)alkyl, (C1-C4)alkyloxycarbonyl(C1-C4)alkyl, (C1-C3)alkyloxycarbonyl(C1-C3)alkyl, (C1-C2)alkyloxycarbonyl(C1-C2)alkyl, etc. In some embodiments, the alkyloxycarbonylalkyl may specifically be ethoxycarbonylethyl, ethoxycarbonylmethyl, methoxycarbonylethyl, methoxycarbonylmethyl, propoxycarbonylpropyl, propoxycarbonylethyl, propoxycarbonylmethyl, etc.

[0088] Optionally, the photocatalyst is an acridinium salt photocatalyst. In some embodiments, the photocatalyst solution is an acetonitrile solution of the photocatalyst, that is, acetonitrile is the solvent.

[0089] Optionally, the general structural formula of the acridinium salt catalyst is as follows:

[0090]

[0091] Wherein, X is any one of tetrafluoroborate anion, hexafluorophosphate anion and perchlorate anion;

[0092] Ar is an aryl group or a substituted aryl group;

[0093] R2 and R3 are each independently any one of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkenyl, heteroalkenyl, cycloalkenyl, heterocycloalkenyl, alkynyl, heteroalkynyl, cycloalkynyl, heterocycloalkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, alkenylalkyl, alkynylalkyl, and cyanoalkyl.

[0094] Optionally, the additives include water and an oxidizing agent.

[0095] When the reaction substrate is primary alkyl ethylbenzene, the capture agent is benzylidenemalononitrile, the photocatalyst is an acridinium salt catalyst, and the additives include water and an oxidant, the reaction mechanism of the photocatalytic reaction is as follows:

[0096]

[0097] In the above chemical reaction formula, acridinium salt catalysts, oxidants, and water work synergistically, among which the photocatalyst can provide better single-electron oxidation, thereby improving the efficiency of carbon-carbon bond breaking during the catalytic reaction. The oxidant and water are used to construct core alcohol intermediates, making the catalytic system less toxic, improving atom utilization and reaction efficiency, and producing fewer by-products; at the same time, the reaction process is made safe and controllable, simplifying the operations during the preparation and production process.

[0098] In some embodiments, the molar ratio of the photocatalyst, the oxidant, and the water is (0.1-20): (0.1-20): (0.2-40). By controlling the content ratio of the photocatalyst, the oxidant, and the water, the reaction has a high catalytic efficiency and improves the yield of the target product. Preferably, the molar ratio of the photocatalyst, the oxidant, and the water is (0.2-20): 2.5: (1-10), which is conducive to obtaining the target product with the highest yield.

[0099] Optionally, the oxidant includes at least one of persulfate, high-valent iodine, quinones, potassium permanganate, peroxides, oxygen and N-fluorobenzenesulfonimide.

[0100] Optionally, the product of the photocatalytic reaction includes one of the following structural formulas:

[0101]

[0102] The product prepared by the above-mentioned method of generating and capturing alkyl free radicals, the addition product prepared by the method has high functionality, making it more diversified in the application of drug intermediate synthesis, functional materials and metal ligands, and can be widely used in organic synthetic chemistry, biochemistry, asymmetric catalysis, pesticide and pharmaceutical research fields, such as for the synthesis of drug intermediates, the preparation of chiral ligands and functional materials, which can effectively reduce the economic cost of the preparation of drug intermediates and functional materials, and the product is environmentally friendly and conducive to application and promotion.

[0103] The following is illustrated by multiple embodiments.

[0104] Example 1

[0105] This embodiment provides a compound 2-(1-phenylpropyl)malononitrile and a preparation method thereof. The structural formula of 2-(1-phenylpropyl)malononitrile is shown in the following molecular structural formula I:

[0106]

[0107] The preparation method of 2-(1-phenylpropyl)malononitrile comprises the following steps:

[0108] S01: The photocatalyst Mes-Acr-PhBF4 (0.01 mmol, 4.6 mg), the capture reagent benzalmalononitrile (0.2 mmol, 30.8 mg) and the oxidant ammonium persulfate (0.5 mmol, 114 mg) were weighed into an oven-dried 8 mL vial equipped with a magnetic star bar, acetonitrile and water (1 mL and 0.1 mL) were added, and then alkylethylbenzene (primary) (0.4 mmol) was added to obtain a reaction solution.

[0109] The structure of alkyl ethylbenzene (primary) is as follows:

[0110]

[0111] S02: The reaction container was degassed and backfilled with argon. The reaction solution was then placed under a 450 nm Kessil lamp for irradiation (40 W). The reaction progress was monitored by TLC to perform a photocatalytic reaction to obtain a mixture.

[0112] S03: The mixture was concentrated and then purified by silica gel flash column chromatography to obtain the target product with a yield of 81%.

[0113] The results of the relevant characterization analysis are 1 H NMR(400MHz,Chloroform-d)δ7.49–7.37(m,3H),7.36–7.30(m,2H),3.92(d,J=6.3H z,1H),3.15(ddd,J=10.9,6.3,5.0Hz,1H),2.23–1.96(m,2H),0.94(t,J=7.3Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ136.53,129.29,128.89,127.86,111.90,48.25,30.05,25.41,11.67.HRMS(ESI-TOF)calculated for C 12 H 12 N2(MH + ):183.0928,found:183.0921.

[0114] This result further confirmed that the molecular structure of the product was exactly as described above.

[0115] Example 2

[0116] This embodiment provides a compound 2-(1-phenyloctyl)malononitrile and a preparation method thereof. The structural formula of 2-(1-phenyloctyl)malononitrile is shown in the following molecular structural formula II:

[0117]

[0118] The preparation method of 2-(1-phenyloctyl)malononitrile comprises the following steps:

[0119] S01: The photocatalyst Mes-Acr-PhBF4 (0.01 mmol, 4.6 mg), the capture reagent benzalmalononitrile (0.2 mmol, 30.8 mg) and the oxidant ammonium persulfate (0.5 mmol, 114 mg) were weighed into an oven-dried 8 mL vial equipped with a magnetic star bar, acetonitrile and water (1 mL and 0.1 mL) were added, and then alkylethylbenzene (primary) (0.4 mmol) was added to obtain a reaction solution.

[0120] The structure of alkyl ethylbenzene (primary) is as follows:

[0121]

[0122] S02: The reaction container was degassed and backfilled with argon. The reaction solution was then placed under a 450 nm Kessil lamp for irradiation (40 W). The reaction progress was monitored by TLC to perform a photocatalytic reaction to obtain a mixture.

[0123] S03: The mixture was concentrated and then purified by silica gel flash column chromatography to obtain the target product with a yield of 75%.

[0124] The results of the relevant characterization analysis are 1 H NMR(400MHz,Chloroform-d)δ7.49–7.37(m,3H),7.37–7.31(m,2H),3.90(d,J=6.2Hz,1H),3.22(dt,J=8 .9,6.5Hz,1H),2.02(td,J=8.4,5.8Hz,2H),1.40–1.29(m,3H),1.27–1.14(m,7H),0.88(t,J=6.9Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ129.28,128.85,127.80,111.91,46.62,32.11,31.65,30.27,29.09,28.92,26.97,22.55,14.04.HRMS(ESI-TOF)calculated for C 17 H 22 N2(MH + ):253.1710,found:253.1709.

[0125] This result further confirmed that the molecular structure of the product was exactly as described above in Molecular Structure II.

[0126] Example 3

[0127] This embodiment provides a compound 2-(2-(4-isobutylphenyl)-1-phenylpropyl)malononitrile and a preparation method thereof. The structural formula of 2-(2-(4-isobutylphenyl)-1-phenylpropyl)malononitrile is shown in the following molecular structural formula III:

[0128]

[0129] The preparation method of 2-(2-(4-isobutylphenyl)-1-phenylpropyl)malononitrile comprises the following steps:

[0130] S01: The photocatalyst Mes-Acr-PhBF4 (0.01 mmol, 4.6 mg), the capture reagent benzalmalononitrile (0.2 mmol, 30.8 mg) and the oxidant sodium persulfate (0.5 mmol, 119 mg) were weighed into an oven-dried 8 mL vial equipped with a magnetic star bar, acetonitrile and water (1 mL and 0.1 mL) were added, and then alkylethylbenzene (primary) (0.4 mmol) was added to obtain a reaction solution.

[0131] The structure of alkyl ethylbenzene (primary) is as follows:

[0132]

[0133] S02: The reaction container was degassed and backfilled with argon. The reaction solution was then placed under a 450 nm Kessil lamp for irradiation (40 W). The reaction progress was monitored by TLC to perform a photocatalytic reaction to obtain a mixture.

[0134] S03: The mixture was concentrated and then purified by silica gel flash column chromatography to obtain the target product with a yield of 85%.

[0135] The results of the relevant characterization analysis are 1 H NMR(400MHz,Chloroform-d)δ7.42(dddd,J=12.5,10.3,6.1,1.9Hz,3H),7.37–7.31(m,2H),3.87(d,J=6.2Hz,1H),3.33(dddd,J=11.0,6 .2,4.5Hz,1H),2.05(ddd,J=13.6,11.3,4.4Hz,1H),1.82–1.71(m,1H),1.45(dpd,J=9.6,6.6,4.3Hz,1H),0.94(dd,J=10.0,6.6Hz,6H). 13C NMR(101MHz,Chloroform-d)δ136.67,129.30,128.88,127.88,111.90,44.67,40.89,30.61,25.23,23.34,21.09.HRMS(ESI-TOF)calculated for C 14 H 16 N2(MH + ):211.1241,found:211.1237.

[0136] This result further confirmed that the molecular structure of the product was exactly as described above in Molecular Structure III.

[0137] Example 4

[0138] This embodiment provides a compound 2-(2-methoxy-1-phenylethyl)malononitrile and a preparation method thereof. The structural formula of 2-(2-methoxy-1-phenylethyl)malononitrile is shown in the following molecular structural formula IV:

[0139]

[0140] The preparation method of 2-(2-methoxy-1-phenylethyl)malononitrile comprises the following steps:

[0141] S01: The photocatalyst Mes-Acr-PhBF4 (0.01 mmol, 4.6 mg), the capture reagent benzalmalononitrile (0.2 mmol, 30.8 mg) and the oxidant potassium persulfate (0.5 mmol, 135 mg) were weighed into an oven-dried 8 mL vial equipped with a magnetic star bar, acetonitrile and water (1 mL and 0.1 mL) were added, and then alkylethylbenzene (primary) (0.4 mmol) was added to obtain a reaction solution.

[0142] The structure of alkyl ethylbenzene (primary) is as follows:

[0143]

[0144] S02: The reaction container was degassed and backfilled with argon. The reaction solution was then placed under a 450 nm Kessil lamp for irradiation (40 W). The reaction progress was monitored by TLC to perform a photocatalytic reaction to obtain a mixture.

[0145] S03: The mixture was concentrated and then purified by silica gel flash column chromatography to obtain the target product with a yield of 57%.

[0146] The results of the relevant characterization analysis are 1H NMR (400MHz, Chloroform-d) δ7.50–7.34 (m, 5H), 4.43 (d, J = 5.9Hz, 1H), 3.90–3.75 (m, 2H), 3.48 (s, 4H). 13 C NMR(101MHz,Chloroform-d)δ134.46,129.25,128.15,112.09,111.61,71.59,59.33,46.44,26.29.HRMS(ESI-TOF)calculated for C 12 H 12 N 2O (MH + ):199.0877,found:199.0872.

[0147] This result further confirmed that the molecular structure of the product was exactly as described above in molecular structure IV.

[0148] Example 5

[0149] This embodiment provides a compound 2-(2-(1,3-dioxoisoindolin-2-yl)-1-phenylethyl)malononitrile and a preparation method thereof. The structural formula of 2-(2-(1,3-dioxoisoindolin-2-yl)-1-phenylethyl)malononitrile is shown in the following molecular structural formula V:

[0150]

[0151] The preparation method of 2-(2-(1,3-dioxoisoindoline-2-yl)-1-phenylethyl)malononitrile comprises the following steps:

[0152] S01: The photocatalyst Mes-Acr-PhBF4 (0.01 mmol, 4.6 mg), the capture reagent benzalmalononitrile (0.2 mmol, 30.8 mg) and the oxidant ammonium persulfate (0.5 mmol, 114 mg) were weighed into an oven-dried 8 mL vial equipped with a magnetic star bar, acetonitrile and water (1 mL and 0.1 mL) were added, and then alkylethylbenzene (primary) (0.4 mmol) was added to obtain a reaction solution.

[0153] The structure of alkyl ethylbenzene (primary) is as follows:

[0154]

[0155] S02: The reaction container was degassed and backfilled with argon. The reaction solution was then placed under a 450 nm Kessil lamp for irradiation (40 W). The reaction progress was monitored by TLC to perform a photocatalytic reaction to obtain a mixture.

[0156] S03: The mixture was concentrated and then purified by silica gel flash column chromatography to obtain the target product with a yield of 48%.

[0157] The results of the relevant characterization analysis are 1 H NMR(400MHz,Chloroform-d)δ7.87(dd,J=5.5,3.1Hz,2H),7.76(dd,J=5.5,3.0Hz,2H),7.42 (m,J=2.8Hz,5H),4.27(d,J=7.5Hz,2H),4.17(d,J=6.2Hz,1H),3.92(td,J=7.5,6.2Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ167.94,134.50,133.79,131.49,129.57,129.40,128.04,123.73,44.85,39.69,27.89.HRMS(ESI-TOF)calculated for C 19 H 13 N 3O (MH + ):314.0935,found:314.0938.

[0158] This result further confirmed that the molecular structure of the product was exactly the above molecular structure V.

[0159] Example 6

[0160] This embodiment provides a compound 6,6-dicyano-5-phenylhexylcyclohexanecarboxylate and a preparation method thereof. The structural formula of 6,6-dicyano-5-phenylhexylcyclohexanecarboxylate is shown in the following molecular structural formula VI:

[0161]

[0162] The preparation method of 6,6-dicyano-5-phenylhexylcyclohexanecarboxylate comprises the following steps:

[0163] S01: The photocatalyst Mes-Acr-PhBF4 (0.01 mmol, 4.6 mg), the capture reagent benzalmalononitrile (0.2 mmol, 30.8 mg) and the oxidant potassium persulfate (0.5 mmol, 135 mg) were weighed into an oven-dried 8 mL vial equipped with a magnetic star bar, acetonitrile and water (1 mL and 0.1 mL) were added, and then alkylethylbenzene (primary) (0.4 mmol) was added to obtain a reaction solution.

[0164] The structure of alkyl ethylbenzene (primary) is as follows:

[0165]

[0166] S02: The reaction container was degassed and backfilled with argon. The reaction solution was then placed under a 450 nm Kessil lamp for irradiation (40 W). The reaction progress was monitored by TLC to perform a photocatalytic reaction to obtain a mixture.

[0167] S03: The mixture was concentrated and then purified by silica gel flash column chromatography to obtain the target product with a yield of 46%.

[0168] The results of the relevant characterization analysis are 1 H NMR(400MHz,Chloroform-d)δ7.50–7.35(m,3H),7.35–7.30(m,2H),4.09–3.96(m,2H),3.91(d,J=6.4Hz,1H),3.23(dt,J=8.8,6.5Hz,1H),2. 25(tt,J=11.2,3.6Hz,1H),2.12–2.01(m,2H),1.90–1.79(m,2H),1.78 –1.70(m,2H),1.70–1.57(m,3H),1.45–1.29(m,4H),1.28–1.16(m,3H). 13 C NMR(101MHz,Chloroform-d)δ176.01,136.41,129.37,128.98,127.78,111.83,111.78,63.2 9,46.56,43.17,31.73,30.28,28.98,28.23,25.72,25.41,23.52.HRMS(ESI-TOF)calculated for C 21 H 26 N 2O2 (MH + ):337.1922,found:337.1924.

[0169] This result further confirmed that the molecular structure of the product was exactly as described above.

[0170] Example 7

[0171] This embodiment provides a compound 6,6-dicyano-5-phenylhexyl-3,7-dimethyloctanoate and a preparation method thereof. The structural formula of 6,6-dicyano-5-phenylhexyl-3,7-dimethyloctanoate is shown in the following molecular structural formula VII:

[0172]

[0173] The preparation method of 6,6-dicyano-5-phenylhexyl-3,7-dimethyloctanoate comprises the following steps:

[0174] S01: The photocatalyst Mes-Acr-PhBF4 (0.01 mmol, 4.6 mg), the capture reagent benzalmalononitrile (0.2 mmol, 30.8 mg) and the oxidant ammonium persulfate (0.5 mmol, 114 mg) were weighed into an oven-dried 8 mL vial equipped with a magnetic star bar, acetonitrile and water (1 mL and 0.1 mL) were added, and then alkylethylbenzene (primary) (0.4 mmol) was added to obtain a reaction solution.

[0175] The structure of alkyl ethylbenzene (primary) is as follows:

[0176]

[0177] S02: The reaction container was degassed and backfilled with argon. The reaction solution was then placed under a 450 nm Kessil lamp for irradiation (40 W). The reaction progress was monitored by TLC to perform a photocatalytic reaction to obtain a mixture.

[0178] S03: The mixture was concentrated and then purified by silica gel flash column chromatography to obtain the target product with a yield of 57%.

[0179] The results of the relevant characterization analysis are 1 H NMR(500MHz,Chloroform-d)δ7.46–7.34(m,3H),7.34–7.28(m,2H),4.08–3.97(m,2H), 3.89(d,J=6.3Hz,1H),3.21(dt,J=9.0,6.5Hz,1H),2.26(dd,J=14.7,5.9Hz,1H),2.11– 1.98(m,3H),1.89(h,J=6.8Hz,1H),1.66(dddd,J=25.8,12.8,8.5,6.7Hz,2H),1.52(dq ,J=13.3,6.6Hz,1H),1.35–1.22(m,5H),1.20–1.09(m,3H),0.88(dd,J=9.3,6.6Hz,9H). 13C NMR(126MHz,Chloroform-d)δ173.25,136.50,129.40,129.03,127.78,111.83,111.77,63.43,46.64,41.85,3 9.09,36.99,31.79,30.38,30.28,28.27,27.94,24.63,23.62,22.66,22.58,19.73.HRMS(ESI-TOF)calculated forC 24 H 34 N2O2(MH + ):381.2548,found:381.2550.

[0180] This result further confirmed that the molecular structure of the product was exactly as described above in Molecular Structure VII.

[0181] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present application should be included in the protection scope of the present application.

Claims

1. A method for generating and capturing alkyl radicals, characterized in that: The following steps are involved: The primary alkylethylbenzene and the capture agent are subjected to a photocatalytic reaction under photocatalytic conditions; The method for photocatalytically reacting primary alkylethylbenzene and a capture agent under photocatalytic conditions comprises the following steps: The primary alkylethylbenzene, the capture agent, the photocatalyst solution and the additive are mixed and treated, and a photocatalytic reaction is carried out under the irradiation of blue light; The structure of the primary alkyl ethylbenzene is as follows: The R1 is any one of an alkyl group and an alkoxy group; The capture agent is benzylidenemalononitrile, the photocatalyst is Mes-Acr-PhBF4, the additive includes water and an oxidant, and the oxidant is persulfate; The structure of the product of the photocatalytic reaction is as follows:

2. The method for generating and capturing alkyl radicals as claimed in claim 1, wherein: The molar ratio of the photocatalyst, the oxidant and the water is (0.1-20):(0.1-20):(0.2-40).

3. The method for generating and capturing alkyl radicals according to claim 1 or 2, characterized in that: The product of the photocatalytic reaction includes one of the following structural formulas:

Images