Synthetic method and application of aliphatic primary amine compound promoted by visible light

Abstract

The invention belongs to the technical field of organic synthesis methodology, and particularly relates to a visible light promoted aliphatic primary amine compound synthesis method and application, the method uses substituted sulfonium salt and substituted styrene as raw materials, ammonium thiocyanate as an amine source, alkali as an additive, an organic solvent is added, reaction is carried out in inert gas at a certain temperature, and the visible light promoted aliphatic primary amine compound is obtained. Under visible light, under the catalytic action of a metal copper complex, the aliphatic primary amine compound is prepared. The method is mild in reaction condition, safe, green and environment-friendly, can be completed in one step, and accords with atom economy and step economy. The aliphatic amine compound and the derivative thereof prepared by the method are expected to serve as lead compounds to be applied to the research and development fields of anti-tumor and antibacterial drugs and the like.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis methodology, and in particular relates to a synthesis method and application of aliphatic primary amine compounds promoted by visible light. Background Art

[0002] Aliphatic primary amine structures are widely present in the synthesis of natural products, drug molecules, functional molecules and agrochemicals ( Figure 1 ) and can serve as core skeletons and basic building blocks for further conversion into diverse secondary amine, tertiary amine, and heterocyclic structures. Statistics show that over 80% of the top 200 best-selling small molecule drugs in 2018 contained nitrogen heterocycles or nitrogen atoms. Traditional methods for synthesizing primary amines rely primarily on reductive amination, cyano reduction, alcohol dehydrogenation coupling, azide, and allylic amination (Org. Lett., 2022, 4, 2055; Science., 2017, 358, 326). However, these pathways require pre-modification of the substrate with polar groups. Another strategy uses olefins as starting materials and constructs them through methods such as hydroamination, aminohydroxylation, and azidation (Angew. Chem. Int. Ed., 2013, 52, 10830; J. Am. Chem. Soc. 2013, 135, 15746; Angew. Chem. Int. Ed., 2016, 55, 534; Science., 2017, 357, 575). However, these reactions generally require pre-treatment of the nitrogen atom with a protecting group followed by removal of the protecting group, or activation of the olefin with an aromatic substituent. Therefore, the development of simple, efficient, novel, and practical methods for constructing primary amines is of paramount importance and has become a research hotspot in recent years.

[0003] Visible light catalysis uses light to excite electrons to initiate chemical reactions, enabling the breaking and reforming of chemical bonds under mild conditions. Compared to traditional heating reactions, it has the advantages of being green, clean, safe, environmentally friendly, and easy to control. In recent years, visible light catalytic reactions have made continuous breakthroughs in the field of synthetic chemistry. A series of visible light catalytic reaction systems have been discovered and successfully applied to the synthesis of various complex compounds, demonstrating outstanding synthetic value and application potential. It is extremely attractive to apply visible light induction to the synthesis of aliphatic primary amine compounds and to study and develop a practical and environmentally friendly method. Summary of the Invention

[0004] In order to overcome the shortcomings and deficiencies of the prior art, the present invention aims to provide a visible light-promoted synthesis method and application of aliphatic primary amine compounds, which does not require harsh synthesis conditions, can synthesize various aliphatic primary amine compounds and their derivatives in one step, and has high universality for multiple functional groups.

[0005] To achieve the above object, the present invention adopts the following technical solutions:

[0006] A visible light-promoted synthesis method of aliphatic primary amine compounds: using substituted sulfonium salts and substituted styrenes as raw materials, ammonium thiocyanate as an amine source, a base as an additive, an organic solvent, reacting under an inert gas and a certain temperature, and catalyzing a metal copper complex under visible light to obtain aliphatic primary amine compounds.

[0007] A visible light-promoted synthesis method of aliphatic primary amine compounds comprises the following steps:

[0008] (1) At room temperature, a substituted sulfonium salt of Formula I, a substituted styrene of Formula II, ammonium thiocyanate, a base, and a metal catalyst are sequentially added to a reaction tube equipped with a magnetic stirrer and filled with inert gas. Under inert gas conditions, an organic reaction solvent is added using a syringe to form a mixed solution. The reaction solution is irradiated with near-blue light at room temperature to promote the reaction.

[0009] (2) After the reaction is completed, an appropriate amount of deionized water is added to the reaction solution, and the mixture is shaken to ensure uniform mixing. 2 mL of ethyl acetate is used as an extractant for separation and extraction. The crude product is extracted from the reaction solution, the extracts are combined, and the solvent is removed by a rotary evaporator. The residue is purified by silica gel column chromatography (silica gel specification is 200 mesh to 300 mesh, and the eluent is petroleum ether / ethyl acetate to obtain the aliphatic primary amine compound represented by formula III;

[0010]

[0011] Where:

[0012] R1 is selected from one or more of aryl, alkyl, halogen, ester, amide, cyano, methoxy, and hydrogen substituents;

[0013] R2 is selected from one or more of halogen, methyl, hydrogen, methoxy, ethoxy, phenoxy, tert-butyl, ester, and cyano substituents;

[0014] X is selected from one of PF6 and BF4, preferably BF4.

[0015] Furthermore, the base is one of lithium methoxide, sodium methoxide, potassium tert-butoxide, sodium tert-butoxide, sodium ethoxide, and sodium carbonate, preferably lithium methoxide;

[0016] The metal catalyst is one of [Cu(dmp)(BINAP)]PF6 shown in Formula IV, [Cu(dpp)(Xantphos)]Cl shown in Formula V, [Cu(dmp)2]Cl shown in Formula VI, or (rac-BINAP)Cu(MeCN)BF4 shown in Formula VII, preferably (rac-BINAP)Cu(MeCN)BF4 shown in Formula VII;

[0017]

[0018] The inert gas is one of nitrogen or argon, preferably nitrogen;

[0019] The wavelength range of the near-violet light is one of 400nm-500nm, preferably 455nm;

[0020] The light source of the visible light is one of an LED lamp, a mercury lamp, a xenon lamp or sunlight, preferably an LED lamp.

[0021] Furthermore, the amount of the substituted styrene represented by formula II is 1-3 times, preferably 2 times, the amount of the substituted sulfonium salt represented by formula I;

[0022] The amount of ammonium thiocyanate is 2-4 times, preferably 3 times, the amount of the substituted sulfonium salt represented by formula I;

[0023] The amount of the base is 1-3 times, preferably 2 times, the amount of the substituted sulfonium salt represented by formula I;

[0024] The amount of the metal copper complex is 0.05-0.15 times, preferably 0.1 times, of the substituted sulfonium salt represented by formula I;

[0025] The amount of the ligand is 0.05-0.15 times, preferably 0.1 times, of the substituted sulfonium salt represented by formula I;

[0026] The organic solvent is one of dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran, dichloromethane, and n-hexane, preferably dimethyl sulfoxide;

[0027] Furthermore, the synthesis reaction is carried out under atmospheric pressure, and the reaction time is 12h-36h, preferably 18h;

[0028] Further, the reaction formula is:

[0029]

[0030] At room temperature, 0.2 mmol of the sulfonium salt, 0.6 mmol of ammonium thiocyanate, 0.02 mmol of the metal catalyst, and 0.4 mmol of the base in the above reaction formula were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then added to the system using a syringe under nitrogen. The reaction tube was placed 3 cm away from a 45-W blue LED lamp and irradiated with blue light and stirred for 18 hours.

[0031] After the reaction is completed, 2 mL of deionized water is added to the reaction solution and stirred evenly. 2 mL of ethyl acetate is used as the extractant each time to extract the crude product from the reaction solution by liquid phase separation extraction operation. The extracts are combined and the solvent is removed by a rotary evaporator; the residue is purified by a silica gel column to obtain the target product.

[0032] Furthermore, the reaction mechanism of the synthesis is:

[0033] First, the catalyst copper (I) complex (rac-BINAP)Cu(MeCN)BF4 shown in Formula VII is excited by visible light to produce excited state species 2 (-2.29V vs. SCE in acetonitrile), which can reduce the arylthiophene salt I (-1.43V vs. SCE) to generate aryl radical 3 and copper (II) complex 5. Subsequently, the aryl radical 3 undergoes a radical addition reaction with styrene II to form benzyl radical 4. Next, the radical 4 undergoes a single electron transfer reaction with the copper (II) complex 5 to generate benzyl cation 7 and the copper (I) complex, completing the catalytic cycle. In addition, the intermediate benzyl cation 6 is regioselectively nucleophilically captured by thiocyanate to obtain the main product 8. In addition, compound 8 can be converted to the unprotected primary amine product III under alkaline conditions.

[0034] The present invention also includes the application of a visible light-promoted method for synthesizing aliphatic primary amine compounds. The synthesis method can be used to synthesize enzyme inhibitors for treating diabetes, can be used to synthesize proteasome inhibitors for treating cancer, can be used to prepare insect repellents, herbicides and fungicides in agricultural chemicals, and can be used as a lead compound for screening anti-tumor or antiviral biopharmaceuticals.

[0035] Aliphatic primary amine compounds and their derivatives have potential anticancer and antiviral activities, and can also be used as antibacterial and antifungal agents. However, the synthesis methods for these compounds are currently very limited. Therefore, the development of new synthesis methods for such compounds has important application value in the field of medicinal chemistry.

[0036] The effective effects of the visible light-promoted synthesis method of aliphatic primary amine compounds and the application thereof are:

[0037] The present invention does not require harsh reaction conditions and can complete the reaction in a single step. It is suitable for synthesizing various aliphatic primary amine compounds and has high universality for a variety of functional groups on the aromatic ring. There are no special restrictions on the number and type of substituents in the aliphatic primary amine compounds. In addition, the number and type of substituents in the sulfonium salt are not particularly limited. The synthesis method of the present invention has a simple preparation process and apparatus, uses near-blue light as energy, employs an organic solvent as a solvent, has mild reaction conditions, and is environmentally friendly. Because the synthesis method is a one-pot process, it does not require complex pretreatment, is non-toxic, and is environmentally friendly, conforming to the environmental protection concepts of green chemistry and atom economy. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 are examples of bioactive molecules having aliphatic primary amine backbones according to the present invention;

[0039] Figure 2 1 is a reaction mechanism diagram of the synthesis method according to an embodiment of the present invention; DETAILED DESCRIPTION

[0040] The technical solution of the present invention is further described in detail below in conjunction with the embodiments, but the protection scope of the present invention is not limited thereto.

[0041] Example 1:

[0042]

[0043] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (5:1 v / v) as the eluent. 41 mg of the target product was obtained with a yield of 68%. The NMR spectrum data of the obtained product are as follows:

[0044] 1H NMR (500MHz, CDCl3) δ7.58(d,J=7.5Hz,2H),7.52(d,J=8.0Hz,2H),7.43(t,J=8.0Hz,2H),7.34(t,J=7.5Hz,1H),7.30(d,J=8.5Hz,2H ),7.26(d,J=8.5Hz,2H),6.89(d,J=8.5Hz,2H),4.89(t,J=6.5Hz,1H),3.81(s,3H),3.04(d,J=6.5Hz,2H),1.96(s,1H),1.57(s,1H).

[0045] 13 C NMR (125MHz, CDCl3) δ159.1,140.9,139.4,137.3,136.0,129.9,128.7,127.2,127.1,127.0,113.8,74.8,55.3,45.6.

[0046] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 21 H 21 NNaO + :326.1515;Found:326.1519.

[0047] Example 2:

[0048]

[0049] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (3:1 v / v) as the eluent. 58 mg of the target product was obtained with a yield of 71%. The NMR spectrum data of the obtained product are as follows:

[0050] 1 H NMR (500MHz, CDCl3) δ7.39(d,J=7.0Hz,2H),7.30(t,J=8.0Hz,1H),7.23(d,J=8.5Hz,2H),7.19(d,J=8.0Hz,2H),7.08–7.00(m,2H),6.81(d,J=8.5H z,2H),4.81(t,J=6.0Hz,1H),3.73(s,3H),3.71–3.65(m,1H),3.62(s,3H) ),2.96(d,J=6.5Hz,2H),1.93(s,1H),1.55(s,1H),1.45(d,J=7.5Hz,3H).

[0051] 13 C NMR (125MHz, CDCl3) δ174.4,160.7(d,J=246.3Hz),159.1,141.7(d,J=7.5Hz),137.8,136.0,133.7,130.7(d,J=3.8Hz),129.6,12 9.0(d,J=2.5Hz),127.6(d,J=13.1Hz),127.1,123.5(d,J=3.8Hz),115.3(d,J=23.8Hz),113.8,74.9,55.3,52.2,45.7,44.9,18.4.

[0052] 19 F NMR (471 MHz, CDCl3) δ-117.5.

[0053] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 25 H 26 FNNaO3 + :430.1789; Found:430.1795.

[0054] Example 3:

[0055]

[0056] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (5:1 v / v) as the eluent. 44 mg of the target product was obtained with a yield of 57%. The NMR spectrum data of the obtained product are as follows:

[0057] 1 H NMR (500MHz, CDCl3) δ7.33(d,J=9.0Hz,2H),7.17(d,J=8.5Hz,2H),7.05(d,J=8.5Hz,2H),6.83(d,J=8.5Hz ,2H),6.81–6.75(m,4H),4.74(t,J=7.0Hz,1H),3.72(s,3H),2.97–2.79(m,2H),1.94(s,1H),1.58(s,1H).

[0058] 13 C NMR (125MHz, CDCl3) δ159.1,156.6,155.2,135.9,133.6,132.6,130.9,127.1,120.2,119.0,115.4,113.7,74.9,55.2,45.1.

[0059] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+H] + Calcd for C 21 H 21 BrNO2 + :398.0751;Found:398.0759.

[0060] Example 4:

[0061]

[0062] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (3:1 v / v) as the eluent. 49 mg of the target product was obtained with a yield of 77%. The NMR spectrum data of the obtained product are as follows:

[0063] 1 H NMR(500MHz, CDCl3)δ7.41(d,J=7.0Hz,2H),7.35(td,J=7.5,1.5Hz,1H),7.26–7.16(m,5H),7.12(t,J=7.5Hz,1H),7.0 9–7.03(m,1H),6.82(d,J=8.5Hz,2H),4.81(t,J=7.0Hz,1H),3.73(s,3H),3.03–2.91(m,2H),1.85(s,1H),1.63(s,1H).

[0064] 13 C NMR (125MHz, CDCl3) δ160.7 (d, J = 246.0Hz), 159.1, 158.76, 137.7, 136.0, 134.0, 130.7 (d, J = 3.4Hz), 129.6, 129.1 (d, J = 2 .8Hz), 128.9 (d, J = 8.0Hz), 128.8 (d, J = 13.4Hz), 127.1, 124.3 (d, J = 3.6Hz), 116.1 (d, J = 22.8Hz), 113.8, 74.9, 55.3, 45.7.

[0065] 19 F NMR (471 MHz, CDCl3) δ-117.7.

[0066] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C21 H 20 FWf + :344.1421; Found:344.1431.

[0067] Example 5:

[0068]

[0069] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (5:1 v / v) as the eluent. 28 mg of the target product was obtained with a yield of 42%. The NMR spectrum data of the obtained product are as follows:

[0070] 1 H NMR(500MHz, CDCl3)δ7.59(d,J=7.5Hz,2H),7.54(d,J=8.0Hz,2H),7.46–7.38(m,4H),7.37–7.2 9(m,5H),4.92(dd,J=9.0,4.5Hz,1H),3.13–2.98(m,2H),1.95(s,1H),1.56(s,1H),1.33(s,9H).

[0071] 13 C NMR (125MHz, CDCl3) δ150.7,140.9,139.5,137.5,129.9,128.7,127.2,127.1,127.0,125.6,125.4,75.1,45.6,34.5,31.4.

[0072] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 24 H 27 NNa +:352.2036;Found:352.2040.

[0073] Example 6:

[0074]

[0075] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (3:1 v / v) as the eluent. 47 mg of the target product was obtained with a yield of 55%. The NMR spectrum data of the obtained product are as follows:

[0076] 1 H NMR (500MHz, CDCl3) δ7.74(d,J=8.0Hz,2H),7.47(d,J=8.0Hz,2H),7.32–7.23(m,6H),6.89(d,J= 8.5Hz,2H),4.89(t,J=6.5Hz,1H),3.81(s,3H),3.04(d,J=6.5Hz,2H),1.94(s,1H),1.58(s,1H).

[0077] 13 C NMR (125MHz, CDCl3) δ159.2,140.5,138.3,137.9,137.9,136.0,130.1,128.9,127.2,126.9,113.9,92.9,75.0,55.3,45.6.

[0078] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 21 H 20 INNaO + :452.0482;Found:452.0485.

[0079] Example 7:

[0080]

[0081] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (3:1 v / v) as the eluent. 42 mg of the target product was obtained with a yield of 61%. The NMR spectrum data of the obtained product are as follows:

[0082] 1 H NMR (500MHz, CDCl3) δ7.57(d,J=7.5Hz,2H),7.52(d,J=8.0Hz,2H),7.43(t,J=7.5Hz,2H),7.33(t,J=7.5Hz,1H),7.27–7.21(m,2H),6.91–6. 80(m,3H),4.87(t,J=6.5Hz,1H),4.07(q,J=7.0Hz,2H),3.87(s,3H),3.04(d,J=6.5Hz,2H),2.01(s,1H),1.61(s,1H),1.44(t,J=7.0Hz,3H).

[0083] 13 C NMR (125MHz, CDCl3) δ148.7,148.2,140.9,139.4,137.2,136.4,129.9,128.7,127.1,127.0,118.1,111.2,110.5,75.2,64.2,55.9,45.6,14.8.

[0084] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 25 NNaO2+ :370.1778;Found:370.1788.

[0085] Example 8:

[0086]

[0087] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (3:1 v / v) as the eluent. 49 mg of the target product was obtained with a yield of 52%. The NMR spectrum data of the obtained product are: 1 H NMR(500MHz, CDCl3)δ8.14(dd,J=5.0,2.0Hz,1H),7.64–7.47(m,1H),7.26(d,J=8.5H z,2H),7.09(d,J=8.5Hz,2H),6.96–6.82(m,9H),6.74(d,J=8.0Hz,1H),5.68–5.44(m, 1H),4.81(t,J=6.5Hz,1H),4.18(dd,J=10.0,5.0Hz,1H),4.06(dd,J=10.0,4.5Hz,1H) ,3.80(s,3H),2.95(d,J=6.5Hz,2H),1.97(s,1H),1.64(s,1H),1.48(d,J=6.5Hz,3H).

[0088] 13 C NMR (125MHz, CDCl3) δ163.1,159.0,157.1,155.1,150.4,146.7,138.7,136.0,132.1,130 .6,127.1,120.6,117.6,116.7,115.7,113.7,111.7,75.0,71.0,69.3,55.3,45.1,17.0.

[0089] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+H] + Calcd for C 29 H 31 N2O4 + :471.2279; Found:471.2274.

[0090] Example 9:

[0091]

[0092] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (5:1 v / v) as the eluent. 36 mg of the target product was obtained with a yield of 51%. The NMR spectrum data of the obtained product are as follows: 1 H NMR (500MHz, CDCl3) δ7.56–7.51(m,2H),7.48–7.43(m,4H),7.42–7.37(m,4H),7.35–7.27 (m,4H),7.26–7.20(m,3H),6.96(d,J=8.0Hz,2H),3.68(s,2H),1.55(s,1H),1.25(s,1H).

[0093] 13 C NMR (125MHz, CDCl3) δ146.5,140.7,139.5,134.9,131.3,128.7,128.1,127.2,126.9,126.7,126.2,78.0,47.6.

[0094] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 26 H 23 NNa+ :372.1723; Found:372.1729.

[0095] Example 10:

[0096]

[0097] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (3:1 v / v) as the eluent. 47 mg of the target product was obtained with a yield of 55%. The NMR spectrum data of the obtained product are as follows: 1 H NMR(500MHz, CDCl3)δ7.66(dd,J=8.0,1.0Hz,1H),7.37–7.28(m,4H),7.26–7.16(m,3H),6.92–6.81(m,3 H),4.89(t,J=6.5Hz,1H),4.15–3.99(m,2H),3.86(s,3H),3.05(d,J=6.5Hz,2H),1.45(t,J=7.0Hz,3H).

[0098] 13 C NMR (125MHz, CDCl3) δ148.7,148.2,142.3,139.2,137.5,136.4,133.1,131.2,129 .4,129.1,128.6,127.3,122.6,118.0,111.2,110.6,75.1,64.2,56.0,45.8,14.8.

[0099] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+H] + Calcd for C 23 H 25 BrNO2 +:426.1064; Found:426.1070.

[0100] Example 11:

[0101]

[0102] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (5:1 v / v) as the eluent. 23 mg of the target product was obtained with a yield of 40%. The NMR spectrum data of the obtained product are:

[0103] 1 H NMR (500MHz, CDCl3) δ7.58(d,J=7.5Hz,2H),7.53(d,J=7.5Hz,2H),7.43(t,J=7.0Hz,2H),7.37–7.21(m,5H ),7.17(d,J=7.0Hz,2H),4.90(t,J=7.0Hz,1H),3.14–2.95(m,2H),2.35(s,3H),1.95(s,1H),1.57(s,1H).

[0104] 13 C NMR (125MHz, CDCl3) δ140.9,139.5,137.3,137.3,129.9,129.1,128.7,127.2,127.1,127.0,125.8,75.2,45.6,21.1.

[0105] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 21 H 21 NNa + :310.1567;Found:310.1573.

[0106] Example 12:

[0107]

[0108] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (5:1 v / v) as the eluent. 23 mg of the target product was obtained with a yield of 40%. The NMR spectrum data of the obtained product are:

[0109] 1 H NMR (500MHz, CDCl3) δ7.58–7.51(m,2H),7.47–7.37(m,6H),7.36–7.28(m,3H),7.28–7.22(m,1H),7.06( d,J=8.0Hz,2H),3.17(d,J=13.0Hz,1H),3.06(d,J=13.5Hz,1H),1.90(s,1H),1.59(s,3H),1.57(s,1H).

[0110] 13 C NMR (125MHz, CDCl3) δ147.5,140.8,139.4,135.8,131.0,128.7,128.1,127.1,126.9,126.7,126.7,125.0,74.5,50.1,29.4.

[0111] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 21 H 21 NNa + :310.1567;Found:310.1560.

[0112] Example 13:

[0113]

[0114] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (5:1 v / v) as the eluent. 34 mg of the target product was obtained with a yield of 47%. The NMR spectrum data of the obtained product are as follows:

[0115] 1 H NMR (500MHz, CDCl3) δ7.57(d,J=7.0Hz,2H),7.54(d,J=8.0Hz,2H),7.43(t,J=7.5Hz,2H),7.34(t,J=7.5Hz,1H),7.28–7 .22(m,2H),5.33(t,J=7.0Hz,1H),3.36(dd,J=13.5,8.0Hz,1H),3.15(dd,J=13.5,6.0Hz,1H),2.31(s,1H),1.57(s,1H).

[0116] 13 C NMR (125MHz, CDCl3) δ140.6,140.1,135.4,129.6,128.8,127.5,127.4,127.0,67.3,42.8.

[0117] 19 F NMR(471MHz,Chloroform-d)δ-143.3,-154.7,-161.7.

[0118] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+H] + Calcd for C 20 H 15 F5N +:364.1120; Found:364.1127.

[0119] Example 14:

[0120]

[0121] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (3:1 v / v) as the eluent. 50 mg of the target product was obtained with a yield of 68%. The NMR spectrum data of the obtained product are:

[0122] 1 H NMR (500MHz, CDCl3) δ7.48 (dd, J=8.0, 1.5Hz, 2H), 7.42 (td, J=7.5, 2.0Hz, 1H) ,7.33–7.27(m,1H),7.27–7.22(m,2H),7.20(td,J=7.5,1.0Hz,1H),7.17–7.1 1(m,1H),6.92–6.81(m,3H),4.88(t,J=6.5Hz,1H),4.14–4.03(m,2H),3.87(s ,3H),3.05(d,J=6.5Hz,2H),1.98(s,1H),1.57(s,1H),1.44(t,J=7.0Hz,3H).

[0123] 13C NMR (125MHz, CDCl3) δ 159.7 (d, J = 246.1Hz), 148.7, 148.2, 137.6, 136.4, 134.0, 130.6 (d, J = 3.5Hz), 129.6, 129.0 (d, J = 2.6Hz), 128 .8(d,J=8.1Hz),128.7(d,J=13.0Hz),124.3(d,J=3.6Hz),118.0,116.1(d,J=22.8Hz),111.2,110.6,75.1,64.3,55.9,45.7,14.8.

[0124] 19 FNMR (471MHz,CDCl3)δ-118.0.

[0125] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 24 FNNaO2 + :388.1684; Found:388.1676.

[0126] Example 15:

[0127]

[0128] At room temperature, the sulfonium salt (0.2 mmol), ammonium thiocyanate (0.6 mmol), (rac-BINAP)Cu(MeCN)BF4 (0.02 mmol) shown in Figure VII, and lithium methoxide (0.4 mmol) were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. Styrene (0.4 mmol) was added to 2.0 mL of dimethyl sulfoxide and then introduced into the system via syringe under nitrogen. The reaction tube was placed 3 cm from a 45-W blue LED lamp and irradiated with blue light while stirring for 18 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 2 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (3:1 v / v) as the eluent. 47 mg of the target product was obtained with a yield of 61%. The NMR spectrum data of the obtained product are as follows:

[0129] 1H NMR (500MHz, CDCl3) δ7.66 (d, J = 8.0Hz, 1H), 7.38–7.29 (m, 6H), 7.28–7.25 (m, 2H), 7.21–7.17 (m, 1H), 6. 90(d,J=8.5Hz,2H),4.92(t,J=6.5Hz,1H),3.82(s,3H),3.06(d,J=6.0Hz,2H),1.93(s,1H),1.58(s,1H).

[0130] 13 C NMR (125MHz, CDCl3) δ159.1,142.3,139.3,137.6,136.0,133.1,131.3,129.5,129.1,128.6,127.4,127.2,122.6,113.8,74.9,55.3,45.8.

[0131] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 21 H 20 BrNNaO + :404.0621;Found:404.0619.

[0132] In the preparation method of the present invention, the order of addition of various materials and the specific reaction steps can be adjusted by those skilled in the art, making it suitable not only for small-scale preparation in the laboratory but also for large-scale industrial production in chemical plants. In industrial batch production, the specific reaction parameters can be determined by those skilled in the art through experiments.

[0133] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0134] Unless otherwise specified, the reagents and materials used in the following examples can be obtained from commercial sources or synthesized from commercially available raw materials.

[0135] The above embodiments are intended only to illustrate the technical concepts and features of the present invention. Their purpose is to enable those skilled in the art to understand the contents of the present invention and implement them accordingly. They are not intended to limit the scope of protection of the present invention. Any equivalent changes or modifications made based on the essence of the present invention are intended to be covered by the scope of protection of the present invention.

Claims

1. A visible light-promoted synthesis method and application of aliphatic primary amine compounds, characterized in that: Using substituted sulfonium salts and substituted styrenes as raw materials, ammonium thiocyanate as an amine source, a base as an additive, and an organic solvent, the reaction is carried out under an inert gas and a certain temperature, and the aliphatic primary amine compound is prepared under the catalysis of a metal copper complex under visible light.

2. The method for synthesizing a visible light-promoted aliphatic primary amine compound and its application according to claim 1, characterized by comprising the following steps: (1) At room temperature, a substituted sulfonium salt of Formula I, a substituted styrene of Formula II, ammonium thiocyanate, a base, and a metal catalyst are sequentially added to a reaction tube equipped with a magnetic stirrer and filled with inert gas. Under inert gas conditions, an organic reaction solvent is added using a syringe to form a mixed solution. The reaction solution is irradiated with near-blue light at room temperature to promote the reaction. (2) After the reaction is completed, an appropriate amount of deionized water is added to the reaction solution, and the mixture is shaken to ensure uniform mixing. 2 mL of ethyl acetate is used as an extractant for separation and extraction. The crude product is extracted from the reaction solution, the extracts are combined, and the solvent is removed by a rotary evaporator. The residue is purified by silica gel column chromatography (silica gel specification is 200 mesh to 300 mesh, and the eluent is petroleum ether / ethyl acetate to obtain the aliphatic primary amine compound represented by formula III; Where: R1 is selected from one or more of aryl, alkyl, halogen, ester, amide, cyano, methoxy, and hydrogen substituents; R2 is selected from one or more of halogen, methyl, hydrogen, methoxy, ethoxy, phenoxy, tert-butyl, ester, and cyano substituents; X is selected from one of PF6 and BF4.

3. The method for synthesizing a visible light-promoted aliphatic primary amine compound and its application according to claim 1 or 2, characterized in that: The base is one of lithium methoxide, sodium methoxide, potassium tert-butoxide, sodium tert-butoxide, sodium ethoxide, and sodium carbonate; The metal catalyst is one of [Cu(dmp)(BINAP)]PF6 shown in Formula IV, [Cu(dpp)(Xantphos)]Cl shown in Formula V, [Cu(dmp)2]Cl shown in Formula VI, or (rac-BINAP)Cu(MeCN)BF4 shown in Formula VII; The inert gas is one of nitrogen or argon; The wavelength range of the near-violet light is one of 400nm-500nm; The light source of the visible light is one of an LED lamp, a mercury lamp, a xenon lamp or sunlight.

4. The method for synthesizing a visible light-promoted aliphatic primary amine compound and its application according to claim 1 or 2, characterized in that: The amount of the substituted styrene represented by formula II is 1-3 times that of the substituted sulfonium salt represented by formula I; The amount of ammonium thiocyanate is 2-4 times that of the substituted sulfonium salt shown in Formula I; The amount of the base is 1-3 times that of the substituted sulfonium salt shown in Formula I; The amount of the metal copper complex is 0.05-0.15 times that of the substituted sulfonium salt shown in Formula I; The organic solvent is one of dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran, dichloromethane and n-hexane.

5. The method for synthesizing a visible light-promoted aliphatic primary amine compound and its application according to claim 1 or 2, characterized in that: The synthesis reaction is carried out under atmospheric pressure, and the reaction time is 10 h to 30 h.

6. A method for synthesizing a visible light-promoted aliphatic primary amine compound according to any one of claims 1 to 4, and its application in anticancer, antitumor, antifungal, and as a herbicide and bactericide in agricultural chemicals.

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