Cyclohexene compound prepared by Birch type dearomatization method based on photo-induced organic amine catalysis and application of cyclohexene compound

Abstract

The invention discloses a cyclohexene compound prepared by a Birch-type dearomatization method based on light-induced organic amine catalysis and application, and belongs to the technical field of organic synthesis. According to the method, the organic amine which is low in price, easy to obtain and excellent in performance is used as the photocatalyst, and the petroleum aromatic hydrocarbon which is low in price, easy to obtain and rich in source is selectively converted into the cyclohexene mono / alkadiene compound with a high additional value in a high-selectivity mode under the mild condition. The method disclosed by the invention is simple, efficient and low in cost, solves harsh conditions and operation dangers existing in the traditional Birch reduction reaction, avoids dependence on expensive and complex photosensitizers, and overcomes the problems of substrate limitation, poor functional group tolerance and regioselectivity, high cost and the like existing in Birch reduction; and the method completely accords with the economic and environment-friendly green chemical synthesis concept under the current new-quality productivity background, and has a wide application prospect.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a cyclohexene compound prepared by a primary birch type de- aromatization method based on photoinduced organic amine catalysis and application. BACKGROUND

[0002] Aromatic compounds, as important products in petroleum and coal chemical production activities, have wide application value. The traditional birch reduction reaction can convert aromatic hydrocarbons into 1,4-cyclohexadiene with high selectivity, which has a wide variety of structures and high added value, and has been widely concerned and researched by chemists, and has been applied to the fields of natural product synthesis, perfume and pharmaceutical industry. However, the traditional birch reduction reaction usually dissolves alkali metals such as lithium, sodium or potassium in liquid ammonia as a solvated electron reducing agent, and has problems such as harsh reaction conditions, high requirements for reaction equipment, and extremely complicated operation and post-processing. Therefore, it is of great research value and significance to find a mild and efficient birch reduction method.

[0003] To address the issues of Birch reduction, in 2019, Professor Baran's group used an excess of expensive phosphoramidate as an additive to achieve an electrochemically promoted Birch reduction (Science 2019, 363, 838-845.). Subsequently, Koide et al. achieved a Birch reduction under liquid ammonia-free conditions by using an excess of elemental lithium and ethylenediamine (Science 2021, 374, 741-746). In recent years, visible light-promoted organic synthesis chemistry, which converts light energy into chemical energy, has attracted widespread attention and research from academia and industry due to its low energy consumption and high efficiency. König's group (Angew. Chem. Int. Ed. 2019, 58, 14289-14294.), You Shuli's group (Angew. Chem. Int. Ed. 2020, 59, 18062-18067.) and Yu Dagang's group (Nat. Catal. 2021, 4, 304-311.) successfully achieved Birch-type de- aromatization reactions of fused ring compounds and electron-deficient arenes such as naphthalene, anthracene, phenanthrene, etc. using noble metal iridium complexes and organic 4CzIPN as photosensitizers, respectively. Subsequently, Miyake et al. (J. Am. Chem. Soc. 2020, 142, 13573-13581; J. Am. Chem. Soc. 2024, 10.1021 / jacs.4c14669) used a complex organic macromolecule with a complex preparation process as a catalyst to achieve visible light-promoted Birch reduction de- aromatization of monocyclic arenes. However, the reaction time is long and the reaction efficiency is low. Although important progress has been made in light-promoted Birch reduction, there are still some problems and development space worth thinking about in this field, for example: 1) Most of the existing photocatalytic systems rely on noble metal complexes or complex macromolecular photosensitizers with complex preparation processes, resulting in high cost of the catalytic system; 2) Limited by the reducing ability of the photocatalytic system, the reported reaction substrates are mostly limited to low triplet energy fused arenes, and the applicability to high triplet energy monocyclic arenes is poor, and the reaction time is long, the efficiency is low, and the selectivity is poor; 3) Poor functional group tolerance, such as fluorine and chlorine groups with important application value cannot be tolerated. Therefore, it is extremely challenging to develop new and efficient photocatalytic systems for selective de- aromatization of high triplet energy monocyclic arenes to prepare functional group diversity cyclohexene / diene. SUMMARY

[0004] In view of the problems of harsh reaction conditions, high equipment requirements and poor functional group tolerance of traditional Birch reduction reaction, and in view of the problems of high cost and low efficiency of the existing photocatalytic system which depends on noble metal or complex macromolecular photosensitizer, the present application aims to provide a method for selective primary Birch type de- aromatization of monocyclic aromatic hydrocarbons based on light-induced organic amine catalysis, and a cyclohexene compound prepared by the method and application of the cyclohexene compound.

[0005] In order to achieve the above purposes, the present application adopts the following technical solutions: The present application provides a method for primary Birch type de-aromatization of monocyclic aromatic hydrocarbons based on light-induced organic amine catalysis, comprising: under the protection of inert gas, using a monocyclic aromatic hydrocarbon compound as a reaction substrate, adding an organic amine photocatalyst, a base, a reducing agent and a proton source, mixing, and performing photochemical reaction under light irradiation, extraction, washing, concentration and purification to obtain a cyclohexene compound and / or a cyclohexadiene compound. The monocyclic aromatic hydrocarbon compound is a compound substituted with one or more substituents on a benzene ring, and the substituents are selected from hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C6-C14 aryl, 5-14 membered heteroaryl, C1-C12 alkoxy, ester, cyano, amine, phosphate, amide, sulfonyl, carbonyl or halogen. The organic amine photocatalyst is selected from an organic amine compound with photocatalytic activity. The base is selected from an inorganic base or an organic base. The reducing agent is selected from dihydropyridine compounds, amine reducing agents, dihydroarenes, borohydrides or borate esters. The proton source is selected from water, alcohols, dihydroarenes or terpenes.

[0006] Preferably, the organic amine compound includes primary alkylamine, secondary alkylamine, tertiary alkylamine or arylamine.

[0007] Preferably, the inorganic base is selected from any one of sodium carbonate, potassium carbonate, potassium phosphate, cesium carbonate, cesium formate, cesium acetate, sodium methoxide, potassium methoxide and sodium hydroxide; and the organic base is selected from any one of triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, tetramethylguanidine, 1,5-diazabicyclo[4.3.0]non-5-ene, triethylenediamine and pyridine.

[0008] Preferably, the reducing agent is selected from 2,6-dimethyl-1,4-dihydro-3,5-pyridine dicarboxylic acid diethyl ester, iPr2Net, triethylenediamine, 1,4-cyclohexadiene, sodium borohydride, pinacol diboronic acid ester or bispinacol borate. Preferably, the proton source is selected from water, methanol, ethanol, isopropanol, 1,4-cyclohexadiene or gamma-terpinene.

[0009] The solvent is any one of toluene, dichloromethane, acetonitrile, tetrahydrofuran, methyl tert-butyl ether, 1,4-dioxane, N,N-dimethylformamide and dimethyl sulfoxide.

[0010] The molar ratio of the reaction substrate to the organic amine photocatalyst is (2-20):1.

[0011] The molar ratio of the alkali to the reaction substrate is (3-5):1, the molar ratio of the reducing agent to the reaction substrate is (3-4):1, and the molar ratio of the proton source to the reaction substrate is (10-15):1.

[0012] The photochemical reaction conditions are: light wavelength is 365-455 nm, temperature is 25-60℃, and time is 10-24h.

[0013] The extraction agent is ethyl acetate, and the extraction times are 2-4 times.

[0014] The washing conditions are: water and saturated sodium chloride are used for washing in sequence.

[0015] The column chromatography uses petroleum ether and ethyl acetate with a volume ratio of (30-5):1 as the eluent.

[0016] The cyclohexene compounds obtained by the method for photo-induced organic amine catalyzed primary Bich-type de-alkylation of monocyclic aromatic hydrocarbons include cyclohexene monomer compounds and cyclohexene diene compounds; The structural formula of the cyclohexene monomer compound is: The structural formula of the cyclohexene diene compound is: , wherein R 1 is selected from an ester group, a cyano group, an amine group, a phosphoramidate group, an amide group, a sulfonyl group or a carbonyl group; R 2 is selected from hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C6-C14 aryl, 5-14 membered heteroaryl, C1-C12 alkoxy, amine or halogen.

[0017] The structural formula of the cyclohexene monomer compound is: , , , , , , , , , , , , , , , 、 、 、 、 、 、 、 、 、 、 and ; the structural formula of the cyclohexene compound is 、 、 、 、 、 、 、 、 、 and .

[0018] The cyclohexene compound is used for preparing an epoxy compound.

[0019] Preferably, the epoxy compound comprises mono / multi-substituted 7-oxabicyclo[4.1.0]heptane compound.

[0020] Preferably, the specific reaction formula is:

[0021] Compared with the prior art, the present application has the following technical effects: The application provides a method for primary Birch type de- aromatization of monocyclic aromatic hydrocarbons based on light-induced organic amine catalysis, which realizes selective de- aromatization of monocyclic aromatic hydrocarbons under mild conditions by constructing a light-induced organic amine catalytic system, effectively avoids the high risk of traditional liquid ammonia system and the high cost defect of existing photocatalytic system, and improves reaction efficiency and functional group adaptability. Inert gas protection prevents the occurrence of side reactions and the deactivation of photocatalysts by isolating oxygen and moisture, ensuring the stability of the reaction; using cheap and readily available organic amines as photocatalysts can selectively promote the de- aromatization reaction of aromatic compounds to generate cyclohexene and cyclohexadiene compounds, compared with traditional photosensitizers, not only the price is lower, but also the preparation process is simpler, reducing the reaction cost; the aromatic compound significantly expands the substrate application range, solving the problem of incompatible sensitive functional groups such as fluorine and chlorine; the organic amine photocatalyst selects simple organic molecules such as primary, secondary and tertiary alkyl amines or aromatic amines to replace noble metals or complex macromolecules, greatly reducing the catalytic cost, which efficiently absorbs light energy and mediates electron transfer under light, driving the de- aromatization process; the addition of base adjusts the reaction environment, promotes the conversion of intermediates and optimizes the catalytic cycle efficiency; the reducing agent provides the necessary electron source to realize the reduction of the aromatic ring, and the efficient reducing agent such as 2,6-dimethyl-1,4-dihydro-3,5-pyridine dicarboxylic acid diethyl ester ensures the reliability of electron transfer; to obtain the best reaction effect; the proton source supplies protons to complete the hydrogenation step, and the selection of mild proton sources such as water and alcohol avoids strong acid conditions, enhancing the reaction mildness; photochemical reaction uses light energy to replace high temperature and high pressure, so that the reaction is carried out at normal temperature and pressure, simplifying the operation process; the extraction, washing, concentration and purification steps in the post-processing ensure the high-purity separation of the target product. The organic amine photocatalyst in the method is excited under light, cooperates with the reducing agent to provide electrons, and the base and proton source jointly regulate the proton-electron transfer path, efficiently converts monocyclic aromatic hydrocarbons in an inert atmosphere, and finally obtains cyclohexene and cyclohexadiene products through post-processing, which overcomes the defects of narrow substrate range and poor functional group tolerance of the primary Birch reduction reaction, can prepare cyclohexene and cyclohexadiene compounds with diverse structures, and has good compatibility with various functional groups; can realize efficient selective de- aromatization reaction to obtain high-purity target product; the method conforms to the concept of green chemical synthesis, has the dual advantages of economy and environmental protection.

[0022] Furthermore, the choice of solvent directly determines the light energy transfer efficiency, catalyst activity, and stability of reaction intermediates. A microenvironment adapted to the photocatalytic process was constructed, overcoming the low efficiency and selectivity defects caused by solvent mismatch in existing technologies. This method enables efficient processing of high triplet-energy monocyclic aromatic hydrocarbons that are difficult for traditional systems to handle. The limitations of photochemical reaction conditions effectively overcome the kinetic and thermodynamic imbalances in the dearomatization process of monocyclic aromatic hydrocarbons, improving not only the overall controllability of the reaction but also significantly enhancing functional group tolerance, making the method applicable to substrates containing sensitive groups such as ester and cyano groups. By precisely defining the type of extractant and the range of extraction times, the separation process in the post-treatment stage was significantly optimized, ensuring efficient recovery of the target product and effective removal of impurities.

[0023] The cyclohexene compound products prepared by the method provided in this invention offer structurally diverse products with good functional group compatibility, overcoming the limitations of traditional preparation methods. As a direct result of the dearomatization reaction, the cyclohexene compounds achieve efficient conversion under mild conditions through an innovative method, avoiding the use of liquid ammonia and alkali metals in traditional Birch reduction, significantly reducing operational risks and equipment complexity. Furthermore, the compounds comprise two types: cyclohexylmonoolefins and cyclohexyldiolefins. The cyclohexylmonoolefins provide monounsaturated structures, suitable for synthetic scenarios requiring specific reaction sites, while the cyclohexyldiolefins possess diunsaturated properties, facilitating subsequent functionalization modifications. Together, these two types broaden the application scope of the products.

[0024] The application provided by this invention uses cyclohexene compounds as core raw materials. The cyclic olefin structure of these compounds gives them suitable reactivity, making them suitable for participation in epoxidation conversion under mild conditions, thereby reducing dependence on traditional high-energy-consuming reaction conditions. It can conveniently prepare mono / polysubstituted 7-oxabicyclo[4.1.0]heptane compounds that are difficult to prepare and have diverse functional groups. Its value lies in its role as a highly active and multifunctional synthetic building block, playing a key role in drug development, materials science, and basic organic synthesis research. Attached Figure Description

[0025] Figure 1 The image shows the nuclear magnetic resonance (NMR) spectrum of the target compound obtained in Example 1 of this invention, wherein A is the hydrogen NMR spectrum and B is the carbon NMR spectrum. Figure 2 The NMR spectrum of the target compound obtained in Example 7 of this invention is shown, wherein A is the hydrogen NMR spectrum and B is the carbon NMR spectrum. Figure 3 The NMR spectrum of the target compound obtained in Embodiment 10 of the present invention is shown, wherein A is the hydrogen NMR spectrum and B is the carbon NMR spectrum. Figure 4The fluorine NMR spectrum of the target compound obtained in Example 10 of this invention; Figure 5 The image shows the nuclear magnetic resonance (NMR) spectrum of the target compound obtained in Embodiment 11 of this invention, wherein A is the hydrogen NMR spectrum and B is the carbon NMR spectrum. Figure 6 The image shows the nuclear magnetic resonance (NMR) spectrum of the target compound obtained in Example 23 of this invention, wherein A is the hydrogen NMR spectrum and B is the carbon NMR spectrum. Figure 7 The image shows the nuclear magnetic resonance (NMR) spectrum of the target compound obtained in Example 24 of this invention, where A is the hydrogen NMR spectrum and B is the carbon NMR spectrum. Figure 8 The image shows the nuclear magnetic resonance (NMR) spectrum of the target compound obtained in Example 26 of this invention, wherein A is the hydrogen NMR spectrum and B is the carbon NMR spectrum. Figure 9 The image shows the nuclear magnetic resonance (NMR) spectrum of the target compound obtained in Example 27 of this invention, where A is the hydrogen NMR spectrum and B is the carbon NMR spectrum. Figure 10 The phosphorus NMR spectrum of the target compound obtained in Example 27 of this invention; Figure 11 The NMR spectrum of the target compound obtained in Embodiment 28 of the present invention is shown, wherein A is the hydrogen NMR spectrum and B is the carbon NMR spectrum. Figure 12 The image shows the nuclear magnetic resonance (NMR) spectrum of the target compound obtained in Example 37 of this invention, wherein A is the hydrogen NMR spectrum and B is the carbon NMR spectrum. Figure 13 The image shows the NMR spectrum of the target compound obtained in Embodiment 39 of this invention, where A is the hydrogen NMR spectrum and B is the carbon NMR spectrum. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0027] Unless otherwise specified, all test materials and reagents used in the following examples are commercially available.

[0028] Unless otherwise specified in the embodiments, the techniques or conditions described in the literature in this field or in accordance with the product manual may be followed.

[0029] Example 1 Under an argon or air atmosphere, 4-benzylbenzonitrile (0.2 mmol), organic amine photosensitizer (0.02 mmol), reducing agent (0.6 mmol), potassium methoxide (0.7 mmol), and methanol (2 mmol) are added. N,N Dimethylformamide (1 mL) and a magnetic particle were added to a 10 mL reaction flask, and the reaction was stirred at room temperature under 385 nm light for 18 hours. After the reaction was completed, water was added to quench the reaction, and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed three times with water and once with saturated sodium chloride. The organic phase was concentrated to obtain the crude product. The crude product was purified by column chromatography using petroleum ether:ethyl acetate 30:1 as the eluent to obtain the target product with a yield of 78%.

[0030] 50 mmol scale reaction: Under argon or air atmosphere, 4-benzylbenzonitrile (50 mmol), organic amine photosensitizer (5 mmol), reducing agent (150 mmol), potassium methoxide (175 mmol), methanol (500 mmol), N,N-dimethylformamide (250 mL), and a magnetic stir bar were added to a 500 mL round-bottom flask. The reaction was stirred at room temperature for 24 hours under 385 nm light irradiation. After the reaction was completed, the mixture was quenched with water, extracted three times with ethyl acetate, and the combined organic phases were washed three times with water and once with saturated sodium chloride. The organic phase was concentrated to obtain the crude product. The crude product was purified by column chromatography using petroleum ether and ethyl acetate in a volume ratio of 30:1 to obtain the target product in 67% yield. See Appendix Figure 1 The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.24-7.19 (m, 2H), 7.16-7.07 (m, 3H), 5.36-5.33 (m, 1H), 3.21(s, 2H), 2.72-2.66 (m, 1H), 2.37 - 2.24 (m, 2H), 2.06-1.99 (m, 1H), 1.93-1.74(m, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 139.2, 137.5, 128.9, 128.4, 126.2,122.5, 119.1, 44.0, 28.5, 25.8, 25.7, 24.60. HRMS (ESI) calcd for C 14 H 16 N [M+H] + Theoretical value 198.1283, measured value 198.1285. Product...1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0031] Example 2 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of 4-(4-methylbenzyl)benzonitrile, and the other steps were the same as in Example 1, yielding the target product in 75% yield. The NMR spectral data of the obtained product are as follows: 1 H NMR (400MHz, Chloroform-d) δ 7.12 (d, J=8.8 Hz, 2H), 7.06 (d, J=8.4 Hz, 2H), 5.44-5.41 (m, 1H), 3.25 (s, 2H), 2.79-2.73 (m, 1H), 2.44-2.31 (m, 5H), 2.14-1.84 (m, 4H). 13 C NMR (101 MHz, Chloroform-d) δ 137.65, 136.01, 135.60, 128.96,128.65, 122.42, 118.72, 43.51, 28.36, 25.73, 25.63, 24.51, 20.92. HRMS (ESI)calcd for C 15 H 18 N[M+H] + Theoretical value 212.1434, measured value 212.1427. Product... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0032] Example 3 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of 4-(4-methoxybenzyl)benzonitrile, and the other steps were the same as in Example 1, resulting in a target product yield of 94%. The product was then subjected to… 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0033] Example 4 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of 4-(4-butylbenzyl)benzonitrile, and the other steps were the same as in Example 1, yielding the target product in 70% yield. The obtained product was subjected to... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0034] Example 5 In this embodiment, equimolar amounts of 4-(4-(tert-butyl)benzyl)benzonitrile were used to replace 4-benzylbenzonitrile in Example 1. Other steps were the same as in Example 1, resulting in a target product yield of 81%. The obtained product was subjected to… 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0035] Example 6 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of 4-(furan-2-ylmethyl)benzonitrile, and the other steps were the same as in Example 1, yielding the target product in 86% yield. The obtained product was subjected to... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0036] Example 7 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of 4-(thiophene-2-ylmethyl)benzonitrile, and the other steps were the same as in Example 1, yielding the target product in 80% yield. See Appendix Figure 2 The obtained product is processed 1 H NMR, 13 The CNMR and HRMS confirmation structures are as follows: .

[0037] Example 8 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of 4-nonylbenzonitrile, and the other steps were the same as in Example 1, yielding the target product in 71% yield. The obtained product was subjected to... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0038] Example 9 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of 4-(benzo[d][1,3]dioxo-5-ylmethyl)benzonitrile, and the other steps were the same as in Example 1, resulting in a target product yield of 82%. The obtained product was subjected to... 1 H NMR, 13 The CNMR and HRMS confirmation structures are as follows: .

[0039] Example 10 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of 4-benzyl-3-fluorobenzonitrile, and the other steps were the same as in Example 1, yielding the target product 4-benzyl-3-fluorocyclohexyl-3-ene-1-carbamate in 87% yield. See Appendix Figures 3-4 The obtained product is processed 1 H NMR, 13 C NMR, 19 The structure confirmed by F NMR and HRMS is: .

[0040] Example 11 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of ethyl 4-(4-cyanophenoxy)butyrate, and the other steps were the same as in Example 1, yielding the target product in 48% yield. See Appendix Figure 5 The obtained product is processed 1 H NMR, 13 The CNMR and HRMS confirmation structures are as follows: .

[0041] Example 12 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of 4-(3-phenylpropoxy)benzonitrile, and the other steps were the same as in Example 1, yielding the target product in 53% yield. The obtained product was subjected to... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0042] Example 13 In this embodiment, equimolar amounts of 4-(oxo)benzonitrile were used to replace 4-benzylbenzonitrile in Example 1, while other steps remained the same as in Example 1, yielding the target product in 37% yield. The obtained product was subjected to... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0043] Example 14 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of 4-(2-hydroxyethyl)benzonitrile, and the other steps were the same as in Example 1, resulting in a target product yield of 61%. The obtained product was subjected to... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0044] Example 15 In this embodiment, equimolar amounts of N-((7-(tert-butyl)-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-yl)methyl)-3-(4-cyanophenyl)-N-methylpropionamide were used to replace 4-benzylbenzonitrile in Example 1. Other steps were the same as in Example 1, resulting in a target product yield of 56%. The obtained product was subjected to… 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0045] Example 16 In this embodiment, equimolar amounts of 4-((1S,4R)-4-pentylcyclohexyl)benzonitrile were used to replace 4-benzylbenzonitrile in Example 1. Other steps were the same as in Example 1, resulting in a target product yield of 73%. The obtained product was subjected to… 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0046] Example 17 In this embodiment, equimolar 2-benzylbenzonitrile was used to replace 4-benzylbenzonitrile in Example 1. Other steps were the same as in Example 1, resulting in a target product yield of 89%. The structural formula is as follows. The regioselectivity ratio of the product was 1:1. The obtained product was subjected to… 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0047] Example 18 In this embodiment, equimolar 3-benzylbenzonitrile was used to replace 4-benzylbenzonitrile in Example 1, and the other steps were the same as in Example 1, yielding the target product in 93% yield with a regioselectivity (rr) ratio of 1.2:1. The obtained product was subjected to... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0048] Example 19 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of ethyl 4-methoxybenzoate, and the other steps were the same as in Example 1, resulting in a target product yield of 72%. The obtained product was subjected to... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0049] Example 20 In this embodiment, equimolar amounts of 3-phenylpropyl 4-methoxybenzoate were used to replace 4-benzylbenzonitrile in Example 1, and the other steps were the same as in Example 1, yielding the target product in 78% yield. The obtained product was subjected to... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0050] Example 21 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of 4-fluorophenylethyl 4-methoxybenzoate, and the other steps were the same as in Example 1, yielding the target product in 78% yield. The obtained product was subjected to... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0051] Example 22 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of 4-methoxybenzoic acid menthol ester, and the other steps were the same as in Example 1, yielding the target product in 71% yield. The obtained product was subjected to... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0052] Example 23 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of diacetone galactose 4-methoxybenzoate, and the other steps were the same as in Example 1, yielding the target product in 56% yield. See Appendix. Figure 6 The obtained product is processed 1 HNMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0053] Example 24 In this embodiment, 4-benzylbenzonitrile was replaced with an equimolar amount of chlorophenyl benzoate in Example 1, and the other steps were the same as in Example 1, yielding the target product in 57% yield. See Appendix. Figure 7 The obtained product is processed 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0054] Example 25 In this embodiment, 4-benzylbenzonitrile in Example 1 was replaced with an equimolar amount of benzofuran methyl 5-carboxylic acid. Other steps were the same as in Example 1, yielding a target product with a yield of 54%. The obtained product was subjected to… 1H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0055] Example 26 In this embodiment, equimolar 3-phenylpropyl 1H-indole-6-carboxylic acid ester was used to replace 4-benzylbenzonitrile in Example 1. Other steps were the same as in Example 1, yielding a target product in 63% yield. See Appendix. Figure 8 The obtained product is processed 1 H NMR, 13 The CNMR and HRMS confirmation structures are as follows: .

[0056] Example 27 In this embodiment, 9-10 are replaced with an equimolar amount of diethyl 4-methoxyphenylphosphonate, and the resulting product is subjected to... 1 H NMR, 13 C NMR, 31 The structure confirmed by P NMR and HRMS is: .

[0057] Example 28 In this embodiment, equimolar N-methyl-N,3-diphenylpropionamide was used to replace 4-benzylbenzonitrile in Example 1, 3.5 equivalents of tetrabutylamine fluoride was used to replace potassium methoxide, and the reducing agent was 2.0 equivalents. Other steps were the same as in Example 1, yielding the target product in 68% yield. See Appendix. Figure 11 The obtained product is processed 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0058] Example 29 In this embodiment, equimolar N-methyl-N-phenylcyclobutane formamide replaced 4-benzylbenzonitrile in Example 1, 3.5 equivalents of tetrabutylamine fluoride replaced potassium methoxide, and the reducing agent was 2.0 equivalents. Other steps were the same as in Example 1, yielding the target product in 70% yield. The obtained product was subjected to… 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0059] Example 30 In this embodiment, 4-benzylbenzonitrile was replaced with an equimolar amount of methyl 4-(methyl(phenyl)amino)-4-oxobutyrate in Example 1, potassium methoxide was replaced with 3.5 equivalents of tetrabutylamine fluoride, and the reducing agent was 2.0 equivalents. Other steps were the same as in Example 1, yielding the target product in 41% yield. 1H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0060] Example 31 In this embodiment, equimolar N-phenyl-N-(3-phenylpropyl)propionamide was used to replace 4-benzylbenzonitrile in Example 1, 3.5 equivalents of tetrabutylamine fluoride were used to replace potassium methoxide, and the reducing agent was 2.0 equivalents. Other steps were the same as in Example 1, yielding the target product in 67% yield. The obtained product was subjected to… 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0061] Example 32 In this embodiment, equimolar N-butyl-N,3-diphenylpropionamide replaced 4-benzylbenzonitrile in Example 1, 3.5 equivalents of tetrabutylamine fluoride replaced potassium methoxide, and the reducing agent was 2.0 equivalents. Other steps were the same as in Example 1, yielding the target product in 62% yield. The obtained product was subjected to… 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0062] Example 33 In this embodiment, equimolar N-(4-benzylphenyl)-N-methyl-3-phenylpropionamide was used to replace 4-benzylbenzonitrile in Example 1, 3.5 equivalents of tetrabutylamine fluoride were used to replace potassium methoxide, and the reducing agent was 2.0 equivalents. Other steps were the same as in Example 1, yielding the target product in 60% yield. The obtained product was subjected to… 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0063] Example 34 In this embodiment, equimolar N-(2-hydroxyethyl)-N-phenylacetamide was used to replace 4-benzylbenzonitrile in Example 1, 3.5 equivalents of tetrabutylamine fluoride were used to replace potassium methoxide, and the reducing agent was 2.0 equivalents. Other steps were the same as in Example 1, yielding the target product in 67% yield. The obtained product was subjected to… 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0064] Example 35 In this embodiment, equimolar N-methyl-N-(4-(4-phenylbutane-2-yl)phenyl)acetamide was used to replace 4-benzylbenzonitrile in Example 1, 3.5 equivalents of tetrabutylamine fluoride were used to replace potassium methoxide, and the reducing agent was 2.0 equivalents. Other steps were the same as in Example 1, yielding the target product in 62% yield. The obtained product was subjected to… 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0065] Example 36 In this embodiment, equimolar N-(4-decylphenyl)-N-methylacetamide was used to replace 4-benzylbenzonitrile in Example 1, 3.5 equivalents of tetrabutylamine fluoride were used to replace potassium methoxide, and the reducing agent was 2.0 equivalents. Other steps were the same as in Example 1, resulting in a target product yield of 61%. The obtained product was subjected to… 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0066] Example 37 In this implementation example, equimolar 2-( N Ethyl 2-(4-isobutylphenyl)propionate (-phenylacetamido) replaced 4-benzylbenzonitrile in Example 1, 3.5 equivalents of tetrabutylamine fluoride replaced potassium methoxide, the reducing agent was 2.0 equivalents, and the other steps were the same as in Example 1, yielding the target product in 68% yield. See Appendix Figure 12 The obtained product is processed 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0067] Example 38 In this implementation example, equimolar 2-( N (-phenylacetamido)ethyl 5-(2,5-dimethylphenoxy)-2,2-dimethylvalerate replaced 4-benzylbenzonitrile in Example 1, 3.5 equivalents of tetrabutylamine fluoride replaced potassium methoxide, the reducing agent was 2.0 equivalents, and other steps were the same as in Example 1, yielding the target product in 67% yield. The obtained product was subjected to... 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0068] Example 39 This embodiment, based on Examples 1 to 38, conducts relevant application experiments on the compounds obtained by this invention. The target compound obtained in Example 1 is oxidized to an epoxide product under the oxidation conditions reported in the reference (Chem. Commun., 2003, 1977-1986), with a target yield of 90%. See Appendix. Figure 13 The obtained product is processed 1 H NMR, 13 The structure confirmed by 1C NMR and HRMS is: .

[0069]

[0070] In summary, taking the target cyclohexene compound obtained in Example 1 as an example, under standard oxidation conditions, it was efficiently and in high yield converted into the corresponding epoxide product, with a target yield as high as 90%. This fully demonstrates that the cyclohexene compound prepared by the invention has high reactivity and purity. As a precursor for the preparation of epoxides, it can achieve efficient and economical conversion, meeting the basic yield requirements for industrial applications. The cyclohexene precursor itself originates from the successful dearomatization of specific substituted aromatic hydrocarbons, which can be smoothly derivatized into epoxides with extremely high yields. This confirms that the cyclohexene intermediate synthesized by the method of the present invention has good functional group compatibility. The functional groups present on its skeleton (involved in Examples 3-38) can all exist stably in the epoxidation step without causing side reactions or catalyst deactivation, thus solving the problem of "poor functional group tolerance" in traditional methods and exhibiting high conversion efficiency. This invention not only solves the three major challenges of photo-induced Birch reduction in terms of cost, substrate universality, and functional group tolerance through an innovative catalytic system, but also successfully synthesizes structurally diverse cyclohexenes. The obtained cyclohexene compounds have great industrial application potential and market value in the preparation of fine chemicals, especially epoxy derivatives.

[0071] The above content is only for illustrating the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solution based on the technical concept proposed in this invention shall fall within the scope of protection of the claims of this invention.

Claims

1. A Birch-type dearomatization method for monocyclic aromatic hydrocarbons based on photoinduced organic amine catalysis, characterized in that, include: Under inert gas protection, monocyclic aromatic compounds are used as reaction substrates. Organic amine photocatalyst, base, reducing agent and proton source are added and mixed. Photochemical reaction is carried out under light irradiation. Extraction, washing, concentration and purification are performed to obtain cyclohexane monoolefin compounds and / or cyclohexane diene compounds. The monocyclic aromatic compound is a compound in which one or more substituents are substituted on the benzene ring. The substituents are selected from hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C6-C14 aryl, 5-14 heteroaryl, C1-C12 alkoxy, ester, cyano, amino, phosphate ester, amide, sulfonyl, carbonyl, or halogen. The organic amine photocatalyst is selected from organic amine compounds with photocatalytic activity; The alkali is selected from inorganic or organic alkalis; The reducing agent is selected from dihydropyridine compounds, amine reducing agents, dihydroaromatics, borohydrides, or borate esters; The proton source is selected from water, alcohols, dihydroaromatics, or terpenes.

2. The Birch-type dearomatization method for monocyclic aromatic hydrocarbons based on photoinduced organic amine catalysis according to claim 1, characterized in that, The solvent is any one of toluene, dichloromethane, acetonitrile, tetrahydrofuran, methyl tert-butyl ether, 1,4-dioxane, N,N-dimethylformamide, and dimethyl sulfoxide.

3. The Birch-type dearomatization method for monocyclic aromatic hydrocarbons based on photoinduced organic amine catalysis according to claim 1, characterized in that, The molar ratio of the reaction substrate to the organic amine photocatalyst is (2~20):

1.

4. The Birch-type dearomatization method for monocyclic aromatic hydrocarbons based on photoinduced organic amine catalysis according to claim 1, characterized in that, The amount of base added is in a molar ratio of (3~5):1 to the reaction substrate, the amount of reducing agent added is in a molar ratio of (3~4):1 to the reaction substrate, and the amount of proton source added is in a molar ratio of (10~15):1 to the reaction substrate.

5. The Birch-type dearomatization method for monocyclic aromatic hydrocarbons based on photoinduced organic amine catalysis according to claim 1, characterized in that, The photochemical reaction conditions are: light wavelength of 365–455 nm, temperature of 25–60 °C, and time of 10–24 h.

6. The Birch-type dearomatization method for monocyclic aromatic hydrocarbons based on photoinduced organic amine catalysis according to claim 1, characterized in that, The extraction process uses ethyl acetate as the extractant and involves 2 to 4 extractions.

7. The Birch-type dearomatization method for monocyclic aromatic hydrocarbons based on photoinduced organic amine catalysis according to claim 1, characterized in that, The washing conditions are as follows: water and saturated sodium chloride are used for washing in sequence; the column chromatography uses petroleum ether and ethyl acetate in a volume ratio of (30~5):1 as eluents.

8. A cyclohexene compound obtained by the Birch-type dearomatization method of monocyclic aromatic hydrocarbons based on photoinduced organic amine catalysis as described in any one of claims 1 to 7, characterized in that, It includes cyclohexane monoolefin compounds and cyclohexane diene compounds; the structural formula of the cyclohexane monoolefin compound is: The structural formula of the cyclohexadiene compound is: , where R 1 Selected from ester, cyano, aminophosphate, amide, sulfonyl, or carbonyl groups; R 2 It is selected from hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C6-C14 aryl, 5-14 heteroaryl, C1-C12 alkoxy, amino or halogen.

9. The cyclohexene compound according to claim 8, characterized in that, The structural formula of the cyclohexyl monoolefin compound is: , , , , , , , , , , , , , , , , , , , , , , , , , and Any one of them; The structural formula of the cyclohexadiene compound is as follows: , , , , , , , , , and Any one of them.

10. The use of the cyclohexene compound of claim 8 or 9 in the preparation of epoxide compounds.

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