Method for photocatalyst-induced reaction of alkyl neopentylbenzene with capture reagent

Abstract

The present application relates to the field of synthetic chemistry technology, and in particular to a method for photocatalyst-induced reaction of alkyl neopentylbenzene with a capture agent, comprising: adding the alkyl neopentylbenzene and the capture agent shown in formula I to a nitroalkane solution containing an acridinium salt photocatalyst, and performing a catalytic reaction under blue light irradiation to obtain one of the following products; wherein the capture agent is selected from benzyl propylene dinitrile, benzenesulfonamide or 1,1-bis(phenylsulfonyl)ethylene. The present application induces carbon-carbon bond cleavage in alkyl neopentylbenzene substrates through single electron transfer, reacts with the capture agent, and the generated alkyl radicals and carbon cations can be captured by the capture agent, thereby obtaining such capture products shown in formula II, formula III or formula IV.

Description

Technical Field

[0001] The present application belongs to the technical field of synthetic chemistry, and in particular relates to a method for photocatalyst-induced reaction of alkyl neopentylbenzene with a capture agent. Background Art

[0002] In recent years, photoredox catalysis has developed rapidly and revolutionized modern free radical chemistry. At the center of these advances, alkyl radicals play an indispensable role in the development of novel synthetic methods under photo / electrochemical catalysis.

[0003] Alkyl radical precursors usually undergo single electron transfer with the help of photoredox catalysts to generate transient alkyl radicals that can participate in various bond-forming processes in a chemo- and stereoselective manner. Some alkyl radical precursors have been developed with a built-in redox group that can narrow the energy gap between the substrate and the excited state of the photosensitizer. Despite these advances, environmentally benign chemical feedstocks for generating alkyl radicals in a precisely controlled manner have not been reported. Summary of the invention

[0004] The purpose of the present application is to provide a method for photocatalyst-induced reaction of alkyl neopentylbenzene with a capture agent, aiming to solve the technical problem of how to use alkyl neopentylbenzene (tertiary) to expand alkyl radical and carbon cation chemistry.

[0005] In order to achieve the above application purpose, the technical solution adopted in this application is as follows:

[0006] The present application provides a method for photocatalyst-induced reaction of alkyl neopentylbenzene with a capture agent, comprising:

[0007] The alkyl neopentylbenzene and the capture agent shown in formula I are added to a nitroalkane solution containing an acridinium salt photocatalyst, and a catalytic reaction is carried out under blue light irradiation to obtain a product shown in formula II, formula III or formula IV;

[0008]

[0009] Wherein, the capture agent is selected from benzyl propylene dinitrile, benzene sulfonamide or 1,1-bis(phenylsulfonyl)ethylene;

[0010] R1, R2, R3 and R4 are independently selected from C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C3-C 20 Cycloalkyl, C3-C 20 Heterocycloalkyl, C2-C 20 Alkenyl, C2-C 20 Heteroalkenyl, C3-C 20Cycloalkenyl, C3-C 20 Heterocycloalkenyl, C2-C 20 Alkynyl, C2-C 20 Heteroalkynyl, C3-C 20 Cycloalkynyl, C3-C 20 Heterocycloalkynyl, C1-C 20 Alkoxy, C6-C 20 Aryl, C4-C 20 Heteroaryl, C6-C 20 Aryloxy, C4-C 20 Heteroaryloxy, C6-C 20 Aryl (C1-C 20 ) alkyl, C4-C20 heteroaryl (C1-C 20 ) alkyl, C2-C 20 Alkenyl (C1-C 20 ) alkyl, C2-C 20 Alkynyl (C1-C 20 ) alkyl, cyano (C1-C 20 ) alkyl, C1-C 20 Alkyloxycarbonyl (C1-C 20 ) Alkyl, silicon C3-C 20 Any one of alkyl, halogen, trifluoromethoxy, sulfonamide and hydrogen atom, or at least two of R2, R3 and R4 are connected to form a cyclic hydrocarbon; and R2, R3 and R4 are not hydrogen atoms.

[0011] The method provided in the present application for photocatalyst-induced reaction of alkyl neopentylbenzene with a capture agent realizes the method for generating alkyl radicals and carbon cations from an unactivated alkyl neopentylbenzene (tertiary) substrate shown in formula I. The substrate shown in formula I is easily oxidized by an acridinium salt photocatalyst under blue light irradiation, and directly breaks to deliver alkyl radicals and carbon cations that can be accepted by various nucleophilic reagents. Therefore, the present application transfers a single electron to an alkyl neopentylbenzene substrate, thereby inducing the cleavage of its carbon-carbon bond and reacting with a capture agent. The capture agent can capture both free radicals and carbon cations, so that the alkyl radicals and carbon cations finally generated can be captured by the capture agent benzyl propylene dinitrile or benzenesulfonamide or 1,1-bis(phenylsulfonyl)ethylene. The reaction process of the method is safe and controllable, which not only simplifies the operation in the production process, but also significantly reduces the production cost of preparing such capture products shown in formula II, formula III or formula IV, and also greatly expands the designability and application prospects of such compounds. DETAILED DESCRIPTION

[0012] 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 below in conjunction with the 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.

[0013] In this application, the term "and / or" describes the association relationship of associated objects, indicating that there may be three relationships. For example, A and / or B can mean: A exists alone, A and B exist at the same time, and B exists alone. A and B can be singular or plural. The character " / " generally indicates that the associated objects are in an "or" relationship.

[0014] It should be understood that in the various embodiments of the present application, the size of the serial numbers of the above-mentioned processes does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0015] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments, and are not intended to limit the present application. The singular forms "a", "said" and "the" used in the embodiments of the present application and the appended claims are also intended to include plural forms, unless the context clearly indicates other meanings.

[0016] The compounds and their derivatives involved in the embodiments 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. Therefore, the compound groups specifically involved in the embodiments of the present invention are described and explained as follows:

[0017] With respect to a "hydrocarbon group", the minimum and maximum carbon atom content in the hydrocarbon group is indicated by a prefix, for example, the prefix (C a -C b )alkyl refers to 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.

[0018] "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. (C a -C b ) Alkoxy refers to any straight or branched, monovalent, saturated aliphatic chain containing an alkyl group of "a" to "b" carbon atoms and bonded to an oxygen atom.

[0019] "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.

[0020] "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.

[0021] "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.

[0022] "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.

[0023] "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.

[0024] "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.

[0025] "Aryl" refers to a cyclic aromatic hydrocarbon, including but not limited to phenyl, naphthyl, anthracenyl, phenanthrenyl and other similar groups.

[0026] "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.

[0027] "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.

[0028] "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.

[0029] "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.

[0030] "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.

[0031] "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.

[0032] "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.

[0033] The present invention provides a method for photocatalyst-induced reaction of alkyl neopentylbenzene with a capture agent, comprising the following steps:

[0034] The alkyl neopentylbenzene and the capture agent shown in formula I are added to a nitroalkane solution containing an acridinium salt photocatalyst, and a catalytic reaction is carried out under blue light irradiation to obtain a product shown in formula II, formula III or formula IV;

[0035]

[0036] Wherein, the capture agent is selected from benzyl propylene dinitrile, benzene sulfonamide or 1,1-bis(phenylsulfonyl)ethylene;

[0037] R1, R2, R3 and R4 are independently selected from C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C3-C20 Cycloalkyl, C3-C 20 Heterocycloalkyl, C2-C 20 Alkenyl, C2-C 20 Heteroalkenyl, C3-C 20 Cycloalkenyl, C3-C 20 Heterocycloalkenyl, C2-C 20 Alkynyl, C2-C 20 Heteroalkynyl, C3-C 20 Cycloalkynyl, C3-C 20 Heterocycloalkynyl, C1-C 20 Alkoxy, C6-C 20 Aryl, C4-C 20 Heteroaryl, C6-C 20 Aryloxy, C4-C 20 Heteroaryloxy, C6-C 20 Aryl (C1-C 20 ) alkyl, C4-C20 heteroaryl (C1-C 20 ) alkyl, C2-C 20 Alkenyl (C1-C 20 ) alkyl, C2-C 20 Alkynyl (C1-C 20 ) alkyl, cyano (C1-C 20 ) alkyl, C1-C 20 Alkyloxycarbonyl (C1-C 20 ) Alkyl, silicon C3-C 20 Any one of alkyl, halogen, trifluoromethoxy, sulfonamide and hydrogen atom, or at least two of R2, R3 and R4 are connected to form a cyclic hydrocarbon; and R2, R3 and R4 are not hydrogen atoms.

[0038] Due to the high oxidation potential of pure alkyl skeletons, the direct generation of alkyl radicals from simple unactivated pure alkyl precursors remains the primary challenge in photoredox catalysis. In an embodiment of the present application, a new method for expanding alkyl radical and carbon cation chemistry using alkyl neopentylbenzene (tertiary) substrates is provided, and the carbon-carbon bond cleavage of a simple pure alkyl skeleton is directly achieved by oxidizing the benzene ring. Specifically, the embodiment of the present application realizes a method for generating alkyl radicals and carbon cations from unactivated alkyl neopentylbenzene (tertiary) shown in formula I, and the substrate shown in formula I is easily oxidized by acridinium salt photocatalysts under blue light irradiation, and directly breaks to deliver alkyl radicals and carbon cations that can be accepted by various nucleophilic reagents. Therefore, the embodiment of the present application induces carbon-carbon bond cleavage of alkyl neopentylbenzene through single electron transfer, and reacts with a capture reagent. The capture reagent can capture both free radicals and carbon cations, and the generated alkyl radicals and carbon cations can be captured by the capture reagent benzyl propylene dinitrile or benzenesulfonamide or 1,1-bis(phenylsulfonyl)ethylene. The reaction process of this method is safe and controllable, which not only simplifies the operation in the production process, but also significantly reduces the production cost of preparing such capture products shown in Formula II, Formula III or Formula IV, and also greatly expands the designability and application prospects of such compounds.

[0039] Specifically, when the capture agent is benzylmalononitrile When the alkyl neopentylbenzene shown in formula I is reacted with the benzyl propylene malononitrile capture reagent under the above conditions to obtain the product shown in formula II.

[0040] When the capture agent is benzenesulfonamide When the alkyl neopentylbenzene shown in formula I is reacted with the benzenesulfonamide capture reagent under the above conditions to obtain a product shown in formula III; the benzenesulfonamide capture reagent can better capture the tert-butyl carbonium ion.

[0041] When the capture agent is 1,1-bis(phenylsulfonyl)ethylene When the alkyl neopentylbenzene shown in formula I is reacted with the 1,1-bis(phenylsulfonyl)ethylene capture reagent under the above conditions to obtain the product shown in formula IV.

[0042] The captured product shown in formula II or formula II or formula IV obtained by the above method of the present application can provide raw materials or reaction intermediates for the synthesis of drug intermediates, the preparation of functional materials and; and because the captured product has high functionality, it can provide diversified choices for the synthesis of drug intermediates, functional materials and applications. It can be widely used in the synthesis of drug intermediates, the preparation of chiral ligands and functional materials, and can effectively reduce the economic cost of the preparation of drug intermediates and functional materials, and provide its environmental friendliness. Therefore, the method of the present application can be widely used in the fields of organic synthetic chemistry, biochemistry, asymmetric catalysis, pesticides and pharmaceutical research, such as in the fields of drug intermediate synthesis and the preparation of functional materials.

[0043] In some embodiments, R2, R3 and R4 are independently selected from C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C3-C 20 Cycloalkyl, C3-C 20 Heterocycloalkyl, C2-C 20 Alkenyl, C2-C 20 Heteroalkenyl, C3-C 20 Cycloalkenyl, C3-C 20 Heterocycloalkenyl, C2-C 20 Alkynyl, C2-C 20 Heteroalkynyl, C3-C 20 Cycloalkynyl, C3-C 20 Heterocycloalkynyl, C1-C 20 Alkoxy, C6-C 20 Aryl, C4-C 20 Heteroaryl, C6-C 20 Aryloxy, C4-C 20 Heteroaryloxy, C6-C 20 Aryl (C1-C 20 ) alkyl, C4-C20 heteroaryl (C1-C 20 ) alkyl, C2-C 20 Alkenyl (C1-C 20 ) alkyl, C2-C 20 Alkynyl (C1-C 20 ) alkyl, cyano (C1-C 20 ) alkyl, C1-C 20 Alkyloxycarbonyl (C1-C 20 ) Alkyl, silicon C3-C 20 Any one of an alkyl group, a halogen group, a trifluoromethoxy group, a sulfonamide group and a hydrogen atom; and R2, R3, and R4 are not hydrogen atoms.

[0044] When R2, R3 and R4 are the same or different C1-C 20 In some embodiments, C1-C20 The alkyl group may be (C1-C 10 )alkyl, (C1-C5)alkyl, (C1-C4)alkyl, (C1-C3)alkyl, (C1-C2)alkyl, etc. In some embodiments, (C1-C 20 ) The alkyl group may specifically be methyl, ethyl, propyl, butyl, isobutyl, pentyl, isopentyl, or the like.

[0045] When R2, R3 and R4 are the same or different (C1-C 20 ) heteroalkyl, in one embodiment, (C1-C 20 ) heteroalkyl can be (C1-C 10 ) heteroalkyl, (C1-C5) heteroalkyl, (C1-C4) heteroalkyl, (C1-C3) heteroalkyl, (C1-C2) heteroalkyl, etc. In some embodiments, the heteroatom may be a halogen, a nitrogen atom, a sulfur atom, etc.

[0046] When R2, R3 and R4 are the same or different (C3-C 20 )cycloalkyl, in one embodiment, (C3-C 20 ) Cycloalkyl can be (C3-C 10 )cycloalkyl, (C3-C5)cycloalkyl, (C3-C4)cycloalkyl, etc. In one embodiment, (C3-C 20 ) Cycloalkyl may be cyclopropyl, cyclobutyl, cyclopentyl, etc.

[0047] When R2, R3 and R4 are the same or different (C3-C 20 )heterocycloalkyl, in one embodiment, (C3-C 20 )Heterocycloalkyl may be (C3-C 10 )heterocycloalkyl, (C3-C 10 )heterocycloalkyl, (C3-C5)heterocycloalkyl, (C3-C4)heterocycloalkyl, etc. In one embodiment, the heteroatom may be a halogen, a nitrogen atom, a sulfur atom, etc.

[0048] When R2, R3 and R4 are the same or different (C2-C 20 )alkenyl, in one embodiment, (C2-C 20 )Alkenyl may be (C3-C 10 )alkenyl, (C3-C5)alkenyl, (C3-C4)alkenyl, (C2-C3)alkenyl, and the like. In some embodiments, (C2-C 20 )Alkenyl may be ethenyl, propenyl, butenyl, pentenyl, etc.

[0049] When R2, R3 and R4 are the same or different (C2-C 20 )heteroalkenyl, in one embodiment, (C2-C20 ) heteroalkenyl can be (C2-C 10 )heteroalkenyl, (C3-C 10 ) heteroalkenyl, (C3-C5) heteroalkenyl, (C3-C4) heteroalkenyl, (C2-C3) heteroalkenyl, etc. In some embodiments, the heteroatom can be a halogen, a nitrogen atom, a sulfur atom, etc.

[0050] When R2, R3 and R4 are the same or different (C3-C 20 )cycloalkenyl, in one embodiment, (C3-C 20 )cycloalkenyl may be (C3-C 10 )cycloalkenyl, (C3-C5)cycloalkenyl, (C3-C4)cycloalkenyl, and the like. In some embodiments, (C3-C 20 ) The cycloalkenyl group may be cyclopropenyl, cyclobutenyl, cyclopentenyl, etc.

[0051] When R2, R3 and R4 are the same or different (C3-C 20 )heterocycloalkenyl, in one embodiment, (C3-C 20 ) The heterocycloalkenyl group may be (C3-C 10 )heterocycloalkenyl, (C3-C5)heterocycloalkenyl, (C3-C4)heterocycloalkenyl, etc. In some embodiments, the heteroatom may be a halogen, a nitrogen atom, a sulfur atom, etc.

[0052] When R2, R3 and R4 are the same or different (C2-C 20 )alkynyl, in one embodiment, (C2-C 20 ) alkynyl may be (C2-C 10 ) alkynyl, (C3-C 10 )alkynyl, (C3-C5)alkynyl, (C3-C4)alkynyl, (C2-C3)alkynyl, and the like. In some embodiments, (C2-C 20 ) Alkynyl may be ethynyl, propynyl, butynyl, pentynyl, etc.

[0053] When R2, R3 and R4 are the same or different (C2-C 20 ) heteroalkynyl, in one embodiment, (C2-C 20 ) heteroalkynyl can be (C2-C 10 ) heteroalkynyl, (C3-C 10 ) heteroalkynyl, (C3-C5) heteroalkynyl, (C3-C4) heteroalkynyl, (C2-C3) heteroalkynyl, etc. In some embodiments, the heteroatom can be a halogen, a nitrogen atom, a sulfur atom, etc.

[0054] When R2, R3 and R4 are the same or different (C3-C 20)cycloalkynyl, in one embodiment, (C3-C 20 ) The cycloalkynyl group may be (C3-C 10 )cycloalkynyl, (C3-C5)cycloalkynyl, (C3-C4)cycloalkynyl, and the like. In some embodiments, (C2-C 20 ) The cycloalkynyl group may be cyclopropynyl, cyclobutynyl, cyclopentynyl, etc.

[0055] When R2, R3 and R4 are the same or different (C3-C 20 )heterocycloalkynyl, in one embodiment, (C3-C 20 ) The heterocycloalkynyl group may be (C3-C 10 ) heterocycloalkynyl, (C3-C5) heterocycloalkynyl, (C3-C4) heterocycloalkynyl, etc. In some embodiments, the heteroatom may be a halogen, a nitrogen atom, a sulfur atom, etc.

[0056] When R2, R3 and R4 are the same or different (C1-C 20 ) alkoxy, in one embodiment, (C1-C 20 ) The alkoxy group may be (C1-C 10 )alkoxy, (C1-C8)alkoxy, (C1-C6)alkoxy, (C1-C4)alkoxy, (C1-C3)alkoxy, (C1-C2)alkoxy. In some embodiments, (C1-C 20 ) Alkoxy may be, but is not limited to, methyloxy, ethyloxy, propyloxy, and the like.

[0057] When R2, R3 and R4 are the same or different aryl groups, the aryl group can be, but is not limited to, a monocyclic aryl group, a polycyclic aryl group, or a condensed ring aryl group. In one embodiment, the aryl group is a monocyclic aryl group. In some embodiments, the aryl group is a phenyl group.

[0058] When R2, R3 and R4 are identical or different substituted aryl groups, the substituted aryl groups may be, but are not limited to, single or multiple substituted phenyl groups at the ortho, meta or para positions. Substituents include, but are not limited to, alkyl, substituted alkyl, halogen, alkoxyamino, nitro, -NR5R6, -NR5-CO-NR6, -OCONR5, -PR5R6, -SOR5, -SO2-R5, -SiR5R6R7, -BR5R6, wherein R5, R6, and R7 may be identical or different as described above. 1 , R 2The groups shown. Wherein, when the substituent is an alkyl group, the alkyl group may be, but not limited to, methyl, ethyl, propyl, butyl, isobutyl; when the substituent is a substituted alkyl group, the substituted alkyl group may be, but not limited to, trifluoromethyl, trichloromethyl, trifluoroethyl, trichloroethyl; when the substituent is a halogen, the halogen may be, but not limited to, fluorine, chlorine, bromine, iodine; when the substituent is an alkoxy group, the alkoxy group may be, but not limited to, methyloxy, ethyloxy, propyloxy. In one embodiment, the substituted aryl group may also be a cyano group (C1-C 10 )alkyl(C3-C8)aryl, substituted(C3-C8)aryl.

[0059] When R2, R3 and R4 are the same or different heteroaryl groups, in one embodiment, the heteroaryl group can be (C3-C8) heteroaryl, furan, or thiophene.

[0060] When R2, R3 and R4 are the same or different substituted heteroaryl groups, in one embodiment, the substituted heteroaryl group can be a substituted (C3-C8) heteroaryl group, an alkoxy-substituted furan group, a (C3-C8) heteroaryl-substituted furan group, or an aliphatic chain-substituted thiophene group.

[0061] When R2, R3 and R4 are the same or different aryloxy groups, in one embodiment, the aryloxy group can be phenoxy, naphthoxy, anthracenyloxy, or phenanthrenyloxy.

[0062] When R2, R3 and R4 are the same or different aromatic groups (C1-C 20 )alkyl, in one embodiment, the aryl (C1-C 20 ) The alkyl group may be an aryl group (C1-C 10 ) alkyl, phenyl (C1-C 10 ) alkyl, phenyl (C1-C5) alkyl, phenyl (C1-C4) alkyl, phenyl (C1-C3) alkyl, phenyl (C1-C2) alkyl, etc. In some embodiments, aryl (C1-C 20 ) The alkyl group may be phenylmethyl, phenylethyl, phenylpropyl, phenylbutyl, phenylisobutyl, phenylpentyl, phenylisopentyl, phenylneopentyl.

[0063] When R2, R3 and R4 are the same or different heteroaryl groups (C1-C 20 )alkyl, in one embodiment, the heteroaryl (C1-C 20 ) alkyl may be a heteroaryl (C1-C 10 ) alkyl, heteroaryl (C1-C 10)alkyl, heteroaryl (C1-C5)alkyl, heteroaryl (C1-C4)alkyl, heteroaryl (C1-C3)alkyl, heteroaryl (C1-C2)alkyl, etc. Among them, the heteroaryl group can be (C3-C8)heteroaryl, furan, pyridine, etc.

[0064] When R2, R3 and R4 are the same or different (C2-C 20 )alkenyl (C1-C 20 )alkyl, in one embodiment, the (C2-C 20 )alkenyl (C1-C 20 ) The alkyl group may be (C2-C 10 )alkenyl (C1-C 10 ), (C2-C5) alkenyl (C1-C3). In certain embodiments, the (C2-C 20 )alkenyl (C1-C 20 ) The alkyl group may be 2-butenyl, 2-pentenyl, 3-hexenyl, 3-heptenyl, or the like.

[0065] When R2, R3, and R4 are the same or different (C2-C 20 ) alkynyl (C1-C 20 )alkyl, in one embodiment, the (C2-C 20 ) alkynyl (C1-C 20 ) The alkyl group may be (C2-C 10 ) alkynyl (C1-C 10 In certain embodiments, the (C2-C5) alkynyl (C1-C3) alkyl. 20 ) alkynyl (C1-C 20 ) The alkyl group may be 2-butynyl, 2-pentynyl, 3-hexynyl, 3-heptynyl, or the like.

[0066] When R2, R3 and R4 are the same or different cyano groups (C1-C 20 )alkyl, in one embodiment, the cyano group (C1-C 20 ) The alkyl group may be a cyano group (C1-C 10 )alkyl, cyano (C1-C5)alkyl, cyano (C1-C4)alkyl, cyano (C1-C3)alkyl, cyano (C1-C2)alkyl, etc. In certain specific embodiments, cyano (C1-C 20 ) The alkyl group may be cyanomethyl, cyanoethyl, cyanopropyl, cyanobutyl, cyanopentyl or the like.

[0067] When R2, R3 and R4 are the same or different alkyloxycarbonylalkyl groups, in one embodiment, the alkyloxycarbonylalkyl group can be (C1-C 10 )alkyloxycarbonyl (C1-C 10)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 group may be ethoxycarbonylethyl, ethoxycarbonylmethyl, methoxycarbonylethyl, methoxycarbonylmethyl, propoxycarbonylpropyl, propoxycarbonylethyl, propoxycarbonylmethyl, etc.

[0068] When at least two of R2, R3 and R4 are linked to form a cyclic hydrocarbon, R3 and R4, or R2 and R4, or R2 and R3 are linked to form a cyclic hydrocarbon, and the remaining one is a separate hydrocarbon group. Alternatively, R2, R3 and R4 are linked together to form a cyclic hydrocarbon.

[0069] In some embodiments, R2, R3 and R4 are independently selected from C1-C 10 Alkyl, C1-C 10 Heteroalkyl, C3-C 10 Cycloalkyl, C3-C 10 Heterocycloalkyl, C2-C 10 Alkenyl, C2-C 10 Heteroalkenyl, C3-C 10 Cycloalkenyl, C3-C 10 Heterocycloalkenyl, C2-C 10 Alkynyl, C2-C 10 Heteroalkynyl, C3-C 10 Cycloalkynyl, C3-C 10 Heterocycloalkynyl, C1-C 10 Alkoxy, C4-C 14 Aryl, C4-C 14 Heteroaryl, C4-C 14 Aryloxy, C4-C 14 Heteroaryloxy, C4-C 14 Aryl (C1-C 10 ) alkyl, C4-C 14 Heteroaryl (C1-C 10 ) alkyl, C2-C 10 Alkenyl (C1-C 10 ) alkyl, C2-C 10 Alkynyl (C1-C 10 ) alkyl, cyano (C1-C 10 ) alkyl, C1-C 10 Alkyloxycarbonyl (C1-C 10 ) alkyl and silicon C3-C 10 Further, R1 is hydrogen, R2, R3 and R4 are independently selected from C1-C 10 Alkyl and C3-C10 Any of the cycloalkyl groups.

[0070] In one embodiment, the structure of the acridinium salt catalyst is as follows:

[0071]

[0072] Wherein, X is tetrafluoroborate anion, hexafluorophosphate anion or perchlorate anion; R4, R5 and R6 are independently selected from C1-C 20 Alkyl, C1-C 20 Heteroalkyl, C3-C 20 Cycloalkyl, C3-C 20 Heterocycloalkyl, C2-C 20 Alkenyl, C2-C 20 Heteroalkenyl, C3-C 20 Cycloalkenyl, C3-C 20 Heterocycloalkenyl, C2-C 20 Alkynyl, C2-C 20 Heteroalkynyl, C3-C 20 Cycloalkynyl, C3-C 20 Heterocycloalkynyl, C1-C 20 Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl (C1-C 20 ) alkyl, heteroaryl (C1-C 20 )alkyl, (C2-C 20 )alkenyl (C1-C 20 )alkyl, (C2-C 20 ) alkynyl (C1-C 20 ) alkyl and cyano (C1-C 20 ) alkyl. The above catalyst has a better photo-oxidation-reduction catalytic effect. In a preferred embodiment of the present application, the photocatalyst is selected from Mes-Acr-PhBF4.

[0073] Furthermore, the molar ratio of the acridinium salt catalyst, the alkyl neopentylbenzene shown in Formula I and the capture agent is (0.1-20):(0.2-40):(1-100). In this case, it is beneficial to obtain the target product.

[0074] In one embodiment, the nitroalkane in the nitroalkane solution is selected from at least one of nitromethane, nitroethane and nitropropane. The alkyl neopentylbenzene and benzyl propionitrile or benzenesulfonamide capture reagent shown in Formula I are added to the nitroalkane solution containing acridine salt photocatalyst. Under blue light irradiation, the nitroalkane solvent can better promote the reaction to obtain the product after the addition of alkyl radicals or carbon cations and the capture reagent. Furthermore, additives are added to the catalytic reaction, specifically water and an oxidant are added. This is conducive to obtaining a high yield of the target product.

[0075] Further, the molar ratio of the acridinium salt catalyst, the oxidant and water is (0.1-20):(0.1-20):(0.2-40). The oxidant is selected from at least one of a high-valent iodine compound, a peroxide compound, a quinone compound, a persulfate, potassium permanganate, oxygen and N-fluorobenzenesulfonimide. For example, the oxidant is selected from ammonium persulfate.

[0076] Furthermore, the method provided in the present application for photocatalyst-induced reaction of alkyl neopentylbenzene with a capture agent is as follows:

[0077]

[0078] The reactant alkyl neopentylbenzene substrate acts as an electrophilic or nucleophilic agent, and can attack substrates such as electron-deficient olefins and electron-rich amines, so that the two reactants undergo an addition reaction. In this way, not only the atomic utilization of the reactants is effectively improved, but also the limitations of the substrates can be broadened, thereby efficiently and greenly preparing target product precursors with high enantioselectivity and extremely wide range, and then obtaining products with potential application value through simple reduction reactions. The above-mentioned synthesis method has structural diversity and can be widely used in the synthesis of drug intermediates, heterocyclic compounds and the preparation of functional materials.

[0079] In the above chemical reaction formula, the synergistic effect of acridinium salt catalyst, oxidant and additive water makes the catalytic system low in toxicity, improves the atomic utilization and reaction efficiency, and produces fewer by-products; at the same time, the reaction process is safe and controllable, simplifying the operation in the preparation and production process. Among them, acridinium salt photocatalysts can provide better single-electron oxidation, thereby improving the efficiency of carbon-carbon bond breaking during the catalytic reaction.

[0080] In order to make the catalytic system play a more effective catalytic effect, in one embodiment, the molar ratio of acridinium salt catalyst, oxidant, and water is (0.1-20): (0.1-20): (0.2-40). In this case, under the synergistic effect of the photocatalyst acridinium salt, oxidant, and water, the reaction has a high catalytic efficiency, which is conducive to improving the yield of the reaction product. Preferably, the molar ratio of acridinium salt catalyst, oxidant, and water is (0.2-20): 2.5: (1-10), in which case, it is conducive to obtaining the target product with the highest yield.

[0081] The novel method for inducing carbon-carbon bond cleavage to generate alkyl radicals provided in the embodiments of the present application has the following advantages: the cleavage method and the captured product have high functional groups and can be widely used in the fields of organic synthetic chemistry, biochemistry, asymmetric catalysis, pesticides and pharmaceutical research, such as in the synthesis of drug intermediates and the preparation of functional materials. The embodiments of the present application obtain any one of the products in the following structural formulas through the above method:

[0082]

[0083] The following describes the invention in conjunction with specific embodiments.

[0084] Example 1

[0085] A 2-(2,2-dimethyl-1-phenylpropyl)malononitrile compound and a preparation method thereof. The structural formula of the 2-(2,2-dimethyl-1-phenylpropyl)malononitrile compound is shown in Formula 1 below:

[0086]

[0087] The preparation method includes: weighing the photocatalyst Mes-Acr-PhBF4 (0.01mmol, 4.6mg), the capture reagent benzalmalononitrile (0.2mmol, 30.8mg) and the oxidant ammonium persulfate (0.5mmol, 114mg) into an oven-dried 8mL vial equipped with a magnetic star bar. Nitromethane and water (1mL and 0.1mL) are added, followed by the addition of alkyl neopentylbenzene (tertiary) The reaction vessel was degassed, backfilled with argon, and then placed under a Kessil lamp at 450 nm (40 W). The reaction progress was monitored by TLC. After completion, the reaction mixture was concentrated and purified by silica gel flash column chromatography to obtain the target product in a yield of 73%.

[0088] The results of the relevant characterization analysis are 1H NMR (400MHz, Chloroform-d) δ7.42 (s, 5H), 4.25 (d, J = 5.7Hz, 1H), 3.04 (d, J = 5.6Hz, 1H), 1.13 (s, 9H). 13 C NMR (101 MHz, Chloroform-d) δ 136.26, 129.32, 128.74, 128.63, 113.20, 113.11, 56.79, 34.96, 28.49, 25.06. This result further confirmed that the molecular structure of the product was exactly the same as the above molecular structure 1.

[0089] Example 2

[0090] A (3,3-dimethylbutane-1,1-methylsulfonyl)benzene compound and a preparation method thereof. The structural formula of the (3,3-dimethylbutane-1,1-methylsulfonyl)benzene compound is shown in Formula 2:

[0091]

[0092] The preparation method includes: weighing the photocatalyst Mes-Acr-PhBF4 (0.01mmol, 4.6mg), the capture agent 1,1-bis(phenylsulfonyl)ethylene (0.2mmol) and the oxidant ammonium persulfate (0.5mmol, 114mg) into an oven-dried 8mL vial equipped with a magnetic star bar. Nitromethane and water (1mL and 0.1mL) are added, followed by the addition of alkyl neopentylbenzene (tertiary) The reaction vessel was degassed, backfilled with argon, and then placed under a Kessil lamp at 450 nm (40 W). The reaction progress was monitored by TLC. After completion, the reaction mixture was concentrated and purified by silica gel flash column chromatography to obtain the target product in a yield of 69%.

[0093] The results of the relevant characterization analysis are 1 H NMR (400MHz, Chloroform-d) δ8.03–7.92(m,4H),7.74–7.68(m,2H),7.63–7.56(m,4H),4.44(t,J=4.0Hz,1H),2.22(d,J=4.1Hz,2H),0.91(s,9H). 13 C NMR (101 MHz, Chloroform-d) δ 138.20, 134.51, 129.95, 129.06, 81.76, 36.62, 31.22, 29.23. This result further confirmed that the molecular structure of the product was exactly the same as the above molecular structure 2.

[0094] Example 3

[0095] A 2-(2,2-dimethyl-1-phenylbutyl)malononitrile compound and a preparation method thereof. The structural formula of the 2-(2,2-dimethyl-1-phenylbutyl)malononitrile compound is shown in Formula 3:

[0096]

[0097] The preparation method includes: weighing the photocatalyst Mes-Acr-PhBF4 (0.01mmol, 4.6mg), the capture reagent benzalmalononitrile (0.2mmol, 30.8mg) and the oxidant ammonium persulfate (0.5mmol, 114mg) into an oven-dried 8mL vial equipped with a magnetic star bar. Nitromethane and water (1mL and 0.1mL) are added, followed by the addition of alkyl neopentylbenzene (tertiary) The reaction vessel was degassed, backfilled with argon, and then placed under a Kessil lamp at 450 nm (40 W). The reaction progress was monitored by TLC. After completion, the reaction mixture was concentrated and purified by silica gel flash column chromatography to obtain the target product in a yield of 70%.

[0098] The results of the relevant characterization analysis are 1 H NMR(400MHz,Chloroform-d)δ7.42(qd,J=5.0,4.5,3.1Hz,5H),4.23(d,J=5.4Hz,1H),3.10(d ,J=5.4Hz,1H),1.42(qd,J=7.4,1.9Hz,2H),1.15(s,3H),1.02(s,3H),0.92(t,J=7.5Hz,3H). 13 C NMR (101 MHz, Chloroform-d) δ 136.00, 129.58, 128.73, 128.62, 113.32, 113.12, 55.09, 37.48, 33.42, 24.85, 24.76, 24.54, 8.19. This result further confirmed that the molecular structure of the product was exactly the same as the above molecular structure 3.

[0099] Example 4

[0100] A 2-((1-ethylcyclohexyl)(phenyl)methyl)malononitrile compound and a preparation method thereof. The structural formula of the 2-((1-ethylcyclohexyl)(phenyl)methyl)malononitrile compound is shown in Formula 4 below:

[0101]

[0102] The preparation method includes: weighing the photocatalyst Mes-Acr-PhBF4 (0.01mmol, 4.6mg), the capture reagent benzalmalononitrile (0.2mmol, 30.8mg) and the oxidant ammonium persulfate (0.5mmol, 114mg) into an oven-dried 8mL vial equipped with a magnetic star bar. Nitromethane and water (1mL and 0.1mL) are added, followed by the addition of alkyl neopentylbenzene (tertiary) The reaction vessel was degassed, backfilled with argon, and then placed under a Kessil lamp at 450 nm (40 W). The reaction progress was monitored by TLC. After completion, the reaction mixture was concentrated and purified by silica gel flash column chromatography to obtain the target product in a yield of 63%.

[0103] The results of the relevant characterization analysis are 1 H NMR(400MHz,Chloroform-d)δ7.43(ddt,J=7.2,5.5,3.1Hz,5H),4.22(d,J=5.1Hz,1H),3.23(d,J =5.1Hz,1H),1.78–1.58(m,5H),1.55–1.42(m,5H),1.28(d,J=1.8Hz,2H),0.88(t,J=7.5Hz,3H). 13 CNMR (101MHz, Chloroform-d)δ135.56,130.01,128.65,128.55,113.60,113.26,52.38,39.69,31.65,31.58,29.72,25.44,24.29,21.29,21.25,7.15. This result further confirmed that the molecular structure of the product is exactly the above-mentioned molecular structure 4.

[0104] Example 5

[0105] A 2-((1-methylcyclohexyl)(phenyl)methyl)malononitrile compound and a preparation method thereof. The structural formula of the 2-((1-methylcyclohexyl)(phenyl)methyl)malononitrile compound is shown in Formula 5 below:

[0106]

[0107] The preparation method includes: weighing the photocatalyst Mes-Acr-PhBF4 (0.01mmol, 4.6mg), the capture reagent benzalmalononitrile (0.2mmol, 30.8mg) and the oxidant ammonium persulfate (0.5mmol, 114mg) into an oven-dried 8mL vial equipped with a magnetic star bar. Nitromethane and water (1mL and 0.1mL) are added, followed by the addition of alkyl neopentylbenzene (tertiary) The reaction vessel was degassed, backfilled with argon, and then placed under a Kessil lamp at 450 nm (40 W). The reaction progress was monitored by TLC. After completion, the reaction mixture was concentrated and purified by silica gel flash column chromatography to obtain the target product in a yield of 65%.

[0108] The results of the relevant characterization analysis are 1 H NMR (400MHz, Chloroform-d) δ7.42(m,5H),4.28(d,J=5.3Hz,1H),3.10(d,J=5.4Hz,1H),1.68–1.36(m,7H),1.35–1.21(m,3H),1.19(s,3H). 13 CNMR(101MHz,Chloroform-d)δ135.74,129.75,128.64,128.54,113.50,113.28,56.7 6,37.33,36.79,36.55,25.66,24.27,21.79,21.45,20.32.HRMS(ESI-TOF)calculated forC 17 H 20 N2(MH + ):251.1554,found:254.1555. This result further confirmed that the molecular structure of the product is exactly the above-mentioned molecular structure 5.

[0109] Example 6

[0110]

[0111] The preparation method of the compound shown in Formula 6 comprises: weighing the photocatalyst Mes-Acr-PhBF4 (0.01 mmol, 4.6 mg), the capture reagent benzylidenemalononitrile (0.2 mmol, 30.8 mg) and the oxidant ammonium persulfate (0.5 mmol, 114 mg) into an oven-dried 8 mL vial equipped with a magnetic star bar. Nitromethane and water (1 mL and 0.1 mL) are added, and then alkyl neopentylbenzene (grade 3) is added. The reaction vessel was degassed, backfilled with argon, and then placed under a Kessil lamp at 450 nm (40 W). The reaction progress was monitored by TLC. After completion, the reaction mixture was concentrated and purified by silica gel flash column chromatography to obtain the target product in 80% yield.

[0112] The results of the relevant characterization analysis are 1H NMR (500MHz, Chloroform-d) δ7.39(m,J=7.5Hz,5H),4.26(d,J=5.4Hz,1H),2.82(d,J=5.3Hz,1H),2.04(q,J=3.2Hz,3H),1.77–1.65(m,9H),1.61(m,3H). 13 C NMR(126MHz,Chloroform-d)δ135.34,129.70,128.63,128.57,113.48,113.33,58.09,40.44,36.58,36.39,28.43,23.79.HRMS(ESI-TOF)calculated for C 20 H 22 N2(MH + ):289.1710,found:289.1709. This result further confirmed that the molecular structure of the product is exactly the above-mentioned molecular structure 6.

[0113] Example 7

[0114] A 2-(1,2-diphenylhexyl)malononitrile compound and a preparation method thereof. The structural formula of the 2-(1,2-diphenylhexyl)malononitrile compound is shown in the following molecular structural formula 7:

[0115]

[0116] The preparation method includes: weighing the photocatalyst Mes-Acr-PhBF4 (0.01mmol, 4.6mg), the trapping agent benzenesulfonamide (1.0mmol) and the oxidant ammonium persulfate (0.5mmol, 114mg) into an oven-dried 8mL vial equipped with a magnetic star bar. Anhydrous nitromethane (1mL) is added, followed by alkyl neopentylbenzene (grade 3) The reaction vessel was degassed, backfilled with argon, and then placed under a 450nm Kessil lamp for irradiation (40W). The reaction progress was monitored by TLC. After completion, the reaction mixture was concentrated and purified by silica gel flash column chromatography to obtain the target product in a yield of 37%.

[0117] Related characterization analysis, the result is a mixture of enantiomers: 1 H NMR (400MHz, Chloroform-d) δ7.97–7.88(m,2H),7.60–7.46(m,3H),4.89(d,J=24.8Hz,1H),1.24(d,J=1.0Hz,9H). 13CNMR(101MHz,Chloroform-d)δ143.43,132.11,128.86,126.92,54.67,30.13.HRMS(ESI-TOF)calculated for C 10 H 15 NO2S(M+H + ):214.0896,found:214.0897. This result further confirmed that the molecular structure of the product is exactly the above-mentioned molecular structure 7.

[0118] 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 photocatalyst-induced reaction of alkyl neopentylbenzene with a capture agent, characterized in that: include: The alkyl neopentylbenzene and the capture agent shown in formula I are added to a nitroalkane solution containing an acridinium salt photocatalyst, and a catalytic reaction is carried out under blue light irradiation to obtain a product shown in formula II; Formula I Formula II Wherein, the capture agent is selected from benzyl malononitrile; the acridinium salt photocatalyst is selected from Mes-Acr-PhBF4; an oxidant is also added to the catalytic reaction, and the oxidant is selected from ammonium persulfate; R1 is hydrogen, R2, R3 and R4 are independently selected from C1-C 10 Alkyl and C3-C 10 Any of the cycloalkyl groups.

2. The method according to claim 1, characterized in that The molar ratio of the acridinium salt catalyst, the alkyl neopentylbenzene represented by formula I and the capture agent is (0.1-20):(0.2-40):(1-100).

3. The method according to claim 1, characterized in that The nitroalkane in the nitroalkane solution is selected from at least one of nitromethane, nitroethane and nitropropane.

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