A method for photocatalytic activation of C(sp 3 -H bonds and construction of C-C bonds with azaheteroarenes

Abstract

The application provides a method for photocatalytic activation of alkane C(sp 3 )‑H bond and construction of C‑C bond with azaheteroarene. The method comprises the following steps: adding an azaheteroarene compound, an alkyl compound and an acid into a solvent to obtain solution A; and irradiating solution A with visible light under an oxygen-containing atmosphere, so that the method is obtained. The method successfully activates the C(sp 3 )‑H bond of the alkyl compound by using photochemical method without introduction of metal catalyst, photocatalyst and strong oxidant, realizes construction of C‑C bond with the azaheteroarene compound, and the whole process is simple, efficient and mild in reaction condition, and the method expands the preparation route of the alkyl-substituted azaheteroarene compound, which is very advantageous for promoting the synthesis route of the coupling reaction of the alkane C(sp 3 )‑H bond and the azaheteroarene.

Description

Technical Field

[0001] This invention belongs to the field of photocatalysis technology, specifically comprising a photocatalytic method for alkane C(sp) 3 A method for activating the -H bond and constructing C-C bonds with nitrogen-containing aromatic hydrocarbons. Background Technology

[0002] Alkyl-substituted aza-aryl compounds possess unique physiological activities and functions, and are widely found in functional molecules such as pharmaceuticals, pesticides, functional materials, and fine chemicals. These are derived through the C(sp) group of alkanes. 3 The activation of H bonds and their azeotropic synthesis of alkyl-substituted azeotropic compounds has the advantages of fewer steps, atom economy, and simple operation. In the existing technology, transition metal catalysis is an effective strategy to realize this reaction. However, this catalytic technology requires the use of noble metal catalysts and specially designed ligands and alkane substrates with directing groups to participate in the reaction, which has high requirements.

[0003] The visible light-involved hydrogen atom transfer strategy is the C(sp) transfer strategy in alkanes. 3 Another effective strategy for activating and azeotropicallyizing α-H bonds. For example, in 2018, David WCMacMillan's group used polytungstate TBADT as a hydrogen atom transfer reagent and photocatalyst, and with the synergistic catalysis of nickel, achieved the azeotropic alkylation of alkane C(sp...)-H bonds. 3 The arylation reaction of alkyl halides with C(sp)-H bonds was also observed. In the same year, Gong Chen's research group utilized a strategy combining the photocatalyst Ru(bpy)3Cl2 with the high-valence iodine oxide PFBI-OH to achieve the arylation of alkyl halides with C(sp)-H bonds. 3 Arylation of alkanes with nitrogen-containing aromatics using stoichiometric K₂S₂O₈ as an oxidant and Ir(ppy)₂(dtbbpy)PF₆ as a photocatalyst under visible light irradiation; In 2021, Li Chaojun's research group achieved arylation of alkanes with nitrogen-containing aromatics using cobalt oxime catalyst and chlorine radical synergistic catalysis. 3 The -H bond of alkanes undergoes coupling reactions with nitrogen-containing aromatic hydrocarbons. However, due to the C(sp) bond in alkanes... 3 The low acidity of the )-H bond, high bond dissociation energy, and lack of π-system coordination with transition metals mean that current technologies utilize the activation of alkane C(sp) bonds. 3 Methods for synthesizing alkyl-substituted nitrogen-containing aromatic compounds via )-H bonds generally require the use of metal catalysts, photocatalysts, and stoichiometric strong oxidants, which greatly limits the application and promotion of this technology. Achieving such reactions under mild conditions has always been a challenge. Summary of the Invention

[0004] To address the aforementioned problems in the existing technology, the present invention aims to provide a photocatalytic method for alkane C(sp) 3 A method for activating the C-H bond and forming a C-C bond with a nitrogen-containing aromatic hydrocarbon. This method utilizes photochemical methods under ambient temperature, atmospheric pressure, and an oxygen-containing atmosphere to activate the C(sp)-H bond of alkyl compounds. 3 The activation of the -H bond enables the construction of C-C bonds with nitrogen-containing aromatic compounds. For the first time, a cross-coupling reaction between two substrates was successfully achieved without the introduction of metal catalysts, photocatalysts, or strong oxidants. The entire process is simple, efficient, economical, and the reaction conditions are mild.

[0005] To achieve the above objectives, the technical solution adopted by the present invention includes:

[0006] This invention discloses a method for photocatalytically constructing C-C bonds, comprising the following steps:

[0007] Aza-aromatic compounds, alkyl compounds, and acids are added to a solvent to obtain solution A;

[0008] Solution A is obtained by irradiating it with visible light under an oxygen-containing atmosphere.

[0009] Furthermore, the acid is selected from one or more of formic acid, acetic acid, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, trifluoroacetic acid, and benzoic acid.

[0010] Furthermore, the aza-aromatic compound is selected from one or more of the structures shown below:

[0011]

[0012] Among them, R1-R 20 They may be the same or different, each independently representing any one of H, OCH3, CH3CH2, (CH3)2CH, (CH3)3C, CH2OH, COOCH3, COOCH2CH3, CF3, F, Cl, Br, NH2, OH, CN, NO2, OCH2Ph, Ph; for example, the azo aromatic hydrocarbon compound may be selected from isoquinoline, 4-chloroisoquinoline, 5-chloroisoquinoline, 6-chloroisoquinoline, 4-bromoisoquinoline, 5-bromoisoquinoline, 6-bromoisoquinoline, 4-phenylisoquinoline, 5-phenylisoquinoline, 5-nitroisoquinoline, 6-cyanoisoquinoline, ethyl 3-carboxylate isoquinoline, 3-methylisoquinoline, 6-methylisoquinoline, 5-methoxyisoquinoline, 6-methoxyisoquinoline, 5-benzyloxyisoquinoline, 5-benzyl ester isoquinoline, 4-chloroquinoline, 4,7-dichloroquinoline, phenazine, etc.

[0013] Furthermore, the alkyl compound is selected from one or more of straight-chain alkanes with C5-C12 carbon atoms, branched-chain alkanes with C5-C12 carbon atoms, and cycloalkanes with C5-C12 carbon atoms; the cycloalkanes can be spirocycloalkanes, fused-chain cycloalkanes, or bridged-chain cycloalkanes; for example, the alkyl compound can be selected from n-pentane, cyclohexane, n-heptane, n-octane, cyclopentane, cycloheptane, norbornane, cyclooctane, cyclododecane, etc.

[0014] Furthermore, the solvent is selected from one or more of acetonitrile, acetone, dimethyl sulfoxide, ethyl acetate, dichloromethane, and 1,2-dichloroethane.

[0015] Furthermore, the reaction system provided by this invention can react as long as there is oxygen. When the oxygen content is low (below 20.9%, i.e., below the proportion of oxygen in the air), the reaction atmosphere will affect the reaction rate. When the oxygen content reaches 20.9% or more, the reaction atmosphere can be considered to have no effect on the reaction rate. The oxygen-containing atmosphere is an air atmosphere or a mixture of inert gas and oxygen in any other proportion.

[0016] Furthermore, the concentration of the alkyl compound in solution A is from 0.001 mol / L to saturation concentration.

[0017] Furthermore, the concentration of the azo aromatic compound in solution A is from 0.001 mol / L to saturation concentration.

[0018] Furthermore, the concentration of the acid in solution A is from 0.001 mol / L to saturation concentration.

[0019] Furthermore, the visible light source is selected from one of LED, xenon lamp, mercury lamp, and sunlight.

[0020] Furthermore, the wavelength range of the visible light is 300-800nm.

[0021] Furthermore, the illumination time of the visible light is 1-48 hours.

[0022] Beneficial effects of this invention:

[0023] This invention discloses a photocatalytic method for alkane C(sp) 3 The method of activating the -H bond and constructing a C-C bond with a nitrogen-containing aromatic hydrocarbon has the following advantages compared to existing technologies:

[0024] 1. This method successfully achieved, for the first time, a cross-coupling reaction between two substrates, alkyl compounds and nitrogen-containing aromatic compounds, without the introduction of metal catalysts, photocatalysts, and strong oxidants.

[0025] 2. This method utilizes photochemical methods to separate the C(sp) of alkane compounds. 3The -H bond is activated, and then reacted with aza-aromatic compounds to achieve the construction of C-C bonds between the two substrates.

[0026] 3. The entire process is simple, efficient, and economical, with mild reaction conditions, expanding the preparation route for alkyl-substituted nitrogen-containing aromatic compounds. This is beneficial for promoting the production of C(sp)-substituted alkanes. 3 The synthetic route involving the coupling reaction of the )-H bond with aza-aromatics is highly advantageous. Attached Figure Description

[0027] The specific embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

[0028] Figure 1 The 1-cyclohexylisoquinoline prepared in Example 1 1 H NMR spectrum;

[0029] Figure 2 The 1-cyclohexylisoquinoline prepared in Example 1 13 C NMR spectrum;

[0030] Figure 3 The 1-(pent-2-yl)isoquinoline and 1-(pent-3-yl)isoquinoline prepared in Example 2 1 H NMR spectrum;

[0031] Figure 4 The 1-(pent-2-yl)isoquinoline and 1-(pent-3-yl)isoquinoline prepared in Example 2 13 C NMR spectrum;

[0032] Figure 5 The 1-(heptane-2-yl)isoquinoline, 1-(heptane-3-yl)isoquinoline and 1-(heptane-4-yl)isoquinoline prepared in Example 3 1 H NMR spectrum;

[0033] Figure 6 The 1-(heptane-2-yl)isoquinoline, 1-(heptane-3-yl)isoquinoline and 1-(heptane-4-yl)isoquinoline prepared in Example 3 13 C NMR spectrum;

[0034] Figure 7 The 1-(octane-2-yl)isoquinoline, 1-(octane-3-yl)isoquinoline and 1-(octane-4-yl)isoquinoline prepared in Example 4 1 H NMR spectrum;

[0035] Figure 8 The 1-(octane-2-yl)isoquinoline, 1-(octane-3-yl)isoquinoline and 1-(octane-4-yl)isoquinoline prepared in Example 4 13 C NMR spectrum;

[0036] Figure 9 The 1-cyclopentylisoquinoline prepared in Example 5 1 H NMR spectrum;

[0037] Figure 10 The 1-cyclopentylisoquinoline prepared in Example 5 13 C NMR spectrum;

[0038] Figure 11 The 1-cycloheptylisoquinoline prepared in Example 6 1 H NMR spectrum;

[0039] Figure 12 The 1-cycloheptylisoquinoline prepared in Example 6 13 C NMR spectrum;

[0040] Figure 13 The 1-((1R,2S,4S)-bicyclo[2.2.1]hept-2-yl)isoquinoline prepared in Example 7 1 H NMR spectrum;

[0041] Figure 14 The 1-((1R,2S,4S)-bicyclo[2.2.1]hept-2-yl)isoquinoline prepared in Example 7 13 C NMR spectrum;

[0042] Figure 15 The 1-cyclooctylisoquinoline prepared in Example 8 1 H NMR spectrum;

[0043] Figure 16 The 1-cyclooctylisoquinoline prepared in Example 8 13 C NMR spectrum;

[0044] Figure 17 1-Cyclododecylisoquinoline prepared in Example 9 1 H NMR spectrum;

[0045] Figure 18 1-Cyclododecylisoquinoline prepared in Example 9 13 C NMR spectrum;

[0046] Figure 19 The 4-chloro-1-cyclohexylisoquinoline prepared in Example 10 1 H NMR spectrum;

[0047] Figure 20 The 4-chloro-1-cyclohexylisoquinoline prepared in Example 10 13 C NMR spectrum;

[0048] Figure 21 The 5-chloro-1-cyclohexylisoquinoline prepared in Example 11 1 H NMR spectrum;

[0049] Figure 22 The 5-chloro-1-cyclohexylisoquinoline prepared in Example 11 13 C NMR spectrum;

[0050] Figure 23 The 6-chloro-1-cyclohexylisoquinoline prepared in Example 12 1 H NMR spectrum;

[0051] Figure 24 The 6-chloro-1-cyclohexylisoquinoline prepared in Example 12 13 C NMR spectrum;

[0052] Figure 25 The 4-bromo-1-cyclohexylisoquinoline prepared in Example 13 1 H NMR spectrum;

[0053] Figure 26 The 4-bromo-1-cyclohexylisoquinoline prepared in Example 13 13 C NMR spectrum;

[0054] Figure 27 The 5-bromo-1-cyclohexylisoquinoline prepared in Example 14 1 H NMR spectrum;

[0055] Figure 28 The 5-bromo-1-cyclohexylisoquinoline prepared in Example 14 13 C NMR spectrum;

[0056] Figure 29 The 6-bromo-1-cyclohexylisoquinoline prepared in Example 15 1 H NMR spectrum;

[0057] Figure 30 The 6-bromo-1-cyclohexylisoquinoline prepared in Example 15 13 C NMR spectrum;

[0058] Figure 31 The 1-cyclohexyl-4-phenylisoquinoline prepared in Example 16 1 H NMR spectrum;

[0059] Figure 32 The 1-cyclohexyl-4-phenylisoquinoline prepared in Example 16 13 C NMR spectrum;

[0060] Figure 33The 1-cyclohexyl-5-phenylisoquinoline prepared in Example 17 1 H NMR spectrum;

[0061] Figure 34 The 1-cyclohexyl-5-phenylisoquinoline prepared in Example 17 13 C NMR spectrum;

[0062] Figure 35 The 1-cyclohexyl-5-nitroisoquinoline prepared in Example 18 1 H NMR spectrum;

[0063] Figure 36 The 1-cyclohexyl-5-nitroisoquinoline prepared in Example 18 13 C NMR spectrum. Detailed Implementation

[0064] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments and accompanying drawings, further clarifies the invention. It should be understood that the described embodiments are merely some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0065] In addition, unless otherwise specified, all raw materials used in this invention can be obtained commercially available. Any range described in this invention includes the end value and any value between the end values, as well as any subrange formed by the end value or any value between the end values.

[0066] Example 1

[0067]

[0068] Add 0.1 mmol isoquinoline, 5 mmol cyclohexane, and 0.12 mmol trifluoroacetic acid to 2.5 mL of acetonitrile to obtain solution A;

[0069] Solution A was irradiated with a 415nm LED at room temperature for 6 hours in an air atmosphere. After the reaction was completed, 1M sodium hydroxide aqueous solution was added to the reaction solution for treatment and the solution was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. The crude product was separated by silica gel (petroleum ether / ethyl acetate = 10:1 elution) column to obtain the product, which was 1-cyclohexylisoquinoline, with a yield of 95%.

[0070] 1H NMR (400MHz, CDCl3) δ8.48(d,J=5.8Hz,1H),8.21(d,J=8.3Hz,1H),7.78(d,J=7.9Hz,1H),7.63(t,J=7.5Hz,1H),7.56(t,J=7.7Hz,1H),7.46( d,J=5.7Hz,1H),3.56(t,J=11.8Hz,1H),1.96(t,J=17.7Hz,4H),1.84(q,J=11.7,10.2Hz,3H),1.53(q,J=13.2Hz,2H),1.40(t,J=12.1Hz,1H).

[0071] Comparative Example 1

[0072]

[0073] Add 0.1 mmol isoquinoline, 5 mmol cyclohexane, and 0.12 mmol trifluoroacetic acid to 2.5 mL of acetone to obtain solution A;

[0074] Solution A was irradiated with a 415nm LED at room temperature for 6 hours in an air atmosphere. After the reaction was completed, 1M sodium hydroxide aqueous solution was added to the reaction solution for treatment and extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. The crude product was separated by silica gel (petroleum ether / ethyl acetate elution = 10:1) column to obtain 1-cyclohexylisoquinoline in a yield of 44%.

[0075] Comparative Example 2

[0076] Add 0.1 mmol isoquinoline, 5 mmol cyclohexane, and 0.12 mmol trifluoroacetic acid to 2.5 mL of methanol to obtain solution A;

[0077] Solution A was irradiated with a 415 nm LED at room temperature for 6 hours in air. After the reaction was complete, 1 M sodium hydroxide aqueous solution was added to the reaction solution for treatment, followed by extraction three times with ethyl acetate. The organic phases were combined, and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. 0.1 mmol of diphenylacetonitrile was added to the crude product as an internal standard for testing. 1 No 1-cyclohexylisoquinoline was observed to be formed by 1H NMR.

[0078] Comparative Example 3

[0079] Add 0.1 mmol isoquinoline, 5 mmol cyclohexane, and 0.12 mmol trifluoroacetic acid to 2.5 mL isopropanol to obtain solution A;

[0080] Solution A was irradiated with a 415 nm LED at room temperature for 6 hours in air. After the reaction was complete, 1 M sodium hydroxide aqueous solution was added to the reaction solution for treatment, followed by extraction three times with ethyl acetate. The organic phases were combined, and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. 0.1 mmol of diphenylacetonitrile was added to the crude product as an internal standard for testing. 1 No 1-cyclohexylisoquinoline was observed to be formed by 1H NMR.

[0081] Comparative Example 4

[0082] 2.5 mL of N,N-dimethylformamide was mixed with 0.1 mmol isoquinoline, 5 mmol cyclohexane, and 0.12 mmol trifluoroacetic acid to obtain solution A;

[0083] Solution A was irradiated with a 415 nm LED at room temperature for 6 hours in air. After the reaction was complete, 1 M sodium hydroxide aqueous solution was added to the reaction solution for treatment, followed by extraction three times with ethyl acetate. The organic phases were combined, and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. 0.1 mmol of diphenylacetonitrile was added to the crude product as an internal standard for testing. 1 No 1-cyclohexylisoquinoline was observed to be formed by 1H NMR.

[0084] Comparative Example 5

[0085]

[0086] Add 0.1 mmol isoquinoline, 5 mmol cyclohexane, and 0.12 mmol trifluoroacetic acid to 2.5 mL of acetonitrile to obtain solution A;

[0087] Solution A was irradiated with a 400 nm LED at room temperature for 6 hours in air. After the reaction was complete, 1 M sodium hydroxide aqueous solution was added to the reaction solution for treatment, followed by extraction three times with ethyl acetate. The organic phases were combined, and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. 0.1 mmol of diphenylacetonitrile was added to the crude product as an internal standard for testing. 1 ¹H NMR yielded 1-cyclohexylisoquinoline in 66% yield.

[0088] Comparative Example 6

[0089]

[0090] Add 0.1 mmol isoquinoline, 5 mmol cyclohexane, and 0.12 mmol concentrated hydrochloric acid to 2.5 mL of acetonitrile to obtain solution A;

[0091] Solution A was irradiated with a 415 nm LED at room temperature for 6 hours in air. After the reaction was complete, 1 M sodium hydroxide aqueous solution was added to the reaction solution for treatment, followed by extraction three times with ethyl acetate. The organic phases were combined, and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. 0.1 mmol of diphenylacetonitrile was added to the crude product as an internal standard for testing. 1 ¹H NMR yielded 1-cyclohexylisoquinoline in 94% yield.

[0092] Comparative Example 7

[0093]

[0094] Add 0.1 mmol isoquinoline, 5 mmol cyclohexane, and 0.12 mmol glacial acetic acid to 2.5 mL of acetonitrile to obtain solution A;

[0095] Solution A was irradiated with a 415 nm LED at room temperature for 6 hours in air. After the reaction was complete, 1 M sodium hydroxide aqueous solution was added to the reaction solution for treatment, followed by extraction three times with ethyl acetate. The organic phases were combined, and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. 0.1 mmol of diphenylacetonitrile was added to the crude product as an internal standard for testing. 1 ¹H NMR yielded 1-cyclohexylisoquinoline in 18% yield.

[0096] Comparative Example 8

[0097]

[0098] Add 0.1 mmol isoquinoline, 5 mmol cyclohexane, and 0.12 mmol benzoic acid to 2.5 mL of acetonitrile to obtain solution A;

[0099] Solution A was irradiated with a 415 nm LED at room temperature for 6 hours in air. After the reaction was complete, 1 M sodium hydroxide aqueous solution was added to the reaction solution for treatment, followed by extraction three times with ethyl acetate. The organic phases were combined, and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. 0.1 mmol of diphenylacetonitrile was added to the crude product as an internal standard for testing. 1 ¹H NMR yielded 1-cyclohexylisoquinoline in a yield of <5%.

[0100] Comparative Example 9

[0101] Add 0.1 mmol isoquinoline, 5 mmol cyclohexane, and 0.12 mmol trifluoroacetic acid to 2.5 mL of acetonitrile to obtain solution A;

[0102] The reaction was carried out in air at room temperature in the dark for 6 hours. After the reaction was completed, 1M sodium hydroxide aqueous solution was added to the reaction solution for treatment and the mixture was extracted three times with ethyl acetate. The organic phases were combined, and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. 0.1 mmol of diphenylacetonitrile was added to the crude product as an internal standard for testing. 1 No 1-cyclohexylisoquinoline was observed to be formed by 1H NMR.

[0103] Comparative Example 10

[0104]

[0105] Add 0.1 mmol isoquinoline, 5 mmol cyclohexane, and 0.12 mmol trifluoroacetic acid to 2.5 mL of acetonitrile to obtain solution A;

[0106] Solution A was irradiated with a 415nm LED at room temperature for 6 hours under a high-purity argon atmosphere. After the reaction was completed, 1M sodium hydroxide aqueous solution was added to the reaction solution for treatment and the solution was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed by rotary evaporation under reduced pressure to obtain 1-cyclohexylisoquinoline with a yield of <5%, which may be due to the presence of trace amounts of oxygen in the reaction tube.

[0107] Comparative Example 11

[0108] Repeat Comparative Example 10, strictly controlling the introduction of oxygen.

[0109] Add 0.1 mmol isoquinoline, 5 mmol cyclohexane, and 0.12 mmol trifluoroacetic acid to 2.5 mL of acetonitrile to obtain solution A;

[0110] Under a high-purity argon atmosphere, solution A was irradiated with a 415 nm LED at room temperature for 6 hours. After the reaction was complete, 1 M sodium hydroxide aqueous solution was added to the reaction solution for treatment, followed by extraction three times with ethyl acetate. The organic phases were combined, and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. 0.1 mmol of diphenylacetonitrile was added to the crude product as an internal standard for testing. 1 ¹H NMR showed no formation of 1-cyclohexylisoquinoline, indicating that the reaction does not occur under an inert atmosphere.

[0111] Examples 2-9

[0112] In Examples 2-9, the operating steps are exactly the same as in Example 1, except that the types of alkane compounds and the reaction time are changed. Other reaction conditions are the same as in Example 1. Please see Table 1 for details.

[0113] Table 1 Summary of experiments in Examples 2-9

[0114]

[0115] As shown in Table 1, the method yields excellent results for both straight-chain alkanes of different chain lengths and cycloalkanes of different molecular weights, indicating that the method provided by this invention has a wide range of substrate options.

[0116] Examples 10-29

[0117] In Examples 10-29, the operating steps are exactly the same as in Example 1, except that the types of azo aromatic compounds and the reaction time are changed. Other reaction conditions are the same as in Example 1. Please see Table 2 for details.

[0118] Table 2 Summary of experiments in Examples 10-29

[0119] Example Azo aromatic compounds Reaction time / hour Yield / % product 10 4-Chloroisoquinoline 12 39 4-Chloro-1-cyclohexylisoquinoline 11 5-Chloroisoquinoline 12 46 5-Chloro-1-cyclohexylisoquinoline 12 6-Chloroisoquinoline 12 63 6-Chloro-1-cyclohexylisoquinoline 13 4-Bromoisoquinoline 7 67 4-Bromo-1-cyclohexylisoquinoline 14 5-Bromoisoquinoline 24 45 5-Bromo-1-cyclohexylisoquinoline 15 6-Bromoisoquinoline 12 59 6-Bromo-1-cyclohexylisoquinoline 16 4-Phenyloisoquinoline 20 29 1-Cyclohexyl-4-phenylisoquinoline 17 5-Phenyloisoquinoline 20 48 1-Cyclohexyl-5-phenylisoquinoline 18 5-Nitroisoquinoline 20 29 1-Cyclohexyl-5-nitroisoquinoline 19 6-Cyanoisoquinoline 24 26 1-Cyclohexylisoquinoline-6-cyano 20 3-Ethyl formate isoquinoline 20 14 Ethyl-1-cyclohexylisoquinoline-3-ester 21 3-Methylisoquinoline 20 38 1-Cyclohexyl-3-methylisoquinoline 22 6-Methylisoquinoline 20 55 1-Cyclohexyl-6-methylisoquinoline 23 5-Methoxyisoquinoline 20 21 1-Cyclohexyl-5-methoxyisoquinoline 24 6-Methoxyisoquinoline 20 16 1-Cyclohexyl-6-methoxyisoquinoline 25 5-Benzyloxyisoquinoline 20 22 5-Benzyloxy-1-cyclohexylisoquinoline 26 5-Benzylisoquinoline 20 56 5-benzoic acid-1-cyclohexylisoquinoline 27 4-Chloroquinoline 24 46 4-Chloro-2-cyclohexylquinoline 28 4,7-Dichloroquinoline 24 60 4,7-Dichloro-2-cyclohexylquinoline 29 Phenylephrine 20 43 6-Cyclohexylphenidine

[0120] Table 2 shows that isoquinolines containing bromine or chlorine substituents at C4, C5, and C6 positions can be converted into the corresponding alkane CH-bonded heteroaromatic products in high yields. When isoquinolines are substituted with electron-depleted groups (phenyl, nitro, cyano, and ester groups, etc.), electron-rich groups (methyl, benzyloxy, and -OCOPh, etc.), or relatively neutral alkyl groups, they can also react with alkanes to give alkane CH-bonded heteroaromatic products, but the yields are lower.

[0121] Example 30 (Scale-up reaction)

[0122]

[0123] Solution A was obtained by adding isoquinoline (900 μL, 7.5 mol), cyclohexane (20 mL, 25 equiv.), trifluoroacetic acid (900 μL, 1.2 equiv.), and acetonitrile (70 mL) to a 150 mL custom-made Pyrex glass illumination tube (5.0 cm inner diameter, 18 cm long) containing a magnetic magnet.

[0124] Solution A was irradiated with a blue LED (λ = 415 nm) at room temperature for 26 hours in an air atmosphere. After the reaction was completed, 1M sodium hydroxide aqueous solution was added to the reaction solution for treatment and the solution was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed by rotary evaporation under reduced pressure. The crude product was purified by silica gel chromatography (eluting with petroleum ether / ethyl acetate) to obtain 1-cyclohexylisoquinoline with a yield of 60% (0.95 g).

[0125] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description. It is impossible to exhaustively list all the implementation methods here. All obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. A method for photocatalytically constructing C-C bonds, characterized in that, The method is performed according to the following steps: Aza-aromatic compounds, alkyl compounds, and acids are added to a solvent to obtain solution A; Solution A is obtained by irradiating it with visible light under an oxygen-containing atmosphere; The acid is selected from one or more of formic acid, acetic acid, hydrochloric acid, phosphoric acid, trifluoroacetic acid, and benzoic acid; The aza-aromatic compound is selected from one or more of the structures shown below: 、 、 ； Among them, R1-R 20 They can be the same or different, each independently representing any one of H, OCH3, CH3CH2, (CH3)2CH, (CH3)3C, CH2OH, COOCH3, COOCH2CH3, CF3, F, Cl, Br, NH2, OH, CN, NO2, OCH2Ph, and Ph; The alkyl compound is selected from one or more of straight-chain alkanes with C5-C12 carbon atoms, branched-chain alkanes with C5-C12 carbon atoms, and cycloalkanes with C5-C12 carbon atoms. The solvent is selected from one or more of acetonitrile, acetone, dimethyl sulfoxide, ethyl acetate, dichloromethane, and 1,2-dichloroethane.

2. The method according to claim 1, characterized in that, The concentration of the alkyl compound in solution A is from 0.001 mol / L to saturation concentration.

3. The method according to claim 1, characterized in that, The concentration of the aza-aromatic compound in solution A is from 0.001 mol / L to saturation concentration.

4. The method according to claim 1, characterized in that, The concentration of the acid in solution A is from 0.001 mol / L to saturation concentration.

5. The method according to claim 1, characterized in that, The visible light source is selected from one of LED, xenon lamp, mercury lamp and sunlight.

6. The method according to claim 1, characterized in that, The illumination time of the visible light is 1-48 hours.

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