A method for preparing beta-heteroaryl ethylamine derivatives using photocatalytic energy transfer

Abstract

The application relates to a method for preparing a beta-heteroaryl ethylamine derivative by utilizing photocatalytic energy transfer, and belongs to the technical field of catalytic synthesis, in particular to a method for preparing a beta-heteroaryl ethylamine derivative by utilizing photocatalytic energy transfer. The application is to solve the technical problems of the existing synthesis method, such as being too complicated, needing pre-activation and expensive metal catalysts. One, an oxime ester compound, an olefin compound and TXT are added into a solvent to obtain a mixed solution; two, the mixed solution obtained in the step one is irradiated by using an LED light source, the solvent is removed by rotary evaporation, and separation and purification are carried out. Compared with the prior art, the application is more green, mild, atom-economical, simple and efficient in a metal-free catalytic energy transfer strategy to construct aryl tertiary amine compounds. The method can be used for preparing a beta-heteroaryl ethylamine derivative.

Description

Technical Field

[0001] The invention belongs to the technical field of catalytic synthesis, and particularly relates to a method for preparing beta-heteroarylethylamine derivatives by utilizing photocatalytic energy transfer. Background Art

[0002] The β-heteroarylethylamine skeleton is commonly found in inhibitory neurotransmitters, natural products, and drug molecules. Its structural formula is as follows:

[0003] Molecules containing this skeleton have remarkable pharmaceutical activity in treating neurological diseases, as antiseptics, and as pain relievers. This has made the construction of β-heteroarylethylamine skeletons a hot topic for synthetic chemists. Among them, utilizing the unique reactivity of the carbon-carbon double bond in olefins to construct β-arylethylamine skeletons is an attractive idea.

[0004] Transition-metal-catalyzed aminoheteroarylation of alkenes, sequentially forming carbon-carbon and carbon-nitrogen bonds, is currently the mainstream strategy for constructing β-heteroarylethylamine skeletons. However, the β-heteroarylethylamine skeleton is primarily used in pharmaceutical synthesis. The use of transition-metal catalysis inevitably results in trace metal residues during the separation process, making subsequent purification of the drug cumbersome and unfavorable for industrialization. Furthermore, the catalytic synthesis is often performed using expensive noble metal catalysts, making this reaction strategy less economical, convenient, and efficient. Therefore, the search for a metal-free, green, mild, convenient, efficient, and environmentally friendly method for synthesizing β-heteroarylethylamine derivatives is a key challenge that needs to be addressed. Summary of the Invention

[0005] The present invention aims to solve the technical problems of the existing synthesis method being too complicated, requiring pre-activation and expensive metal catalysts, and provides a method for preparing β-heteroarylethylamine derivatives by utilizing photocatalytic energy transfer.

[0006] A method for preparing β-heteroarylethylamine derivatives by using photocatalytic energy transfer is specifically carried out according to the following steps:

[0007] 1. adding an oxime ester compound, an olefin compound and TXT into a solvent to obtain a mixed solution;

[0008] 2. Under a nitrogen atmosphere and room temperature, the mixed solution obtained in step 1 is irradiated with an LED light source, and the solvent is removed by rotary evaporation, followed by separation and purification by thin layer chromatography. The obtained product is a β-heteroarylethylamine derivative, thereby completing the preparation;

[0009] The chemical structural formula of the oxime ester compound is:

[0010] The chemical structure of olefin compounds is:

[0011] The chemical structure of β-heteroarylethylamine derivatives is:

[0012] Wherein R is a pyridine group, and R1 is a phenyl group or an alkane group.

[0013] Furthermore, the TXT described in step 1 is a photocatalyst 9-thioxanthone, and its structural formula is:

[0014]

[0015] Furthermore, the ratio of the oxime ester compound to the solvent in step 1 is 0.07-0.1 mmol:1 mL.

[0016] Furthermore, the ratio of the olefin compound to the solvent in step 1 is 0.2-0.4 mmol:1 mL.

[0017] Furthermore, the wavelength of the LED light source in step 2 is 380-400 nm, and the power is 10-50 W.

[0018] Furthermore, the light source irradiation time in step 2 is 3 to 6 hours.

[0019] The present invention utilizes a photocatalytic energy transfer strategy and uses a catalytic amount of 9-thioxanthone as an energy transfer catalyst to transfer energy to the oxime ester so that the oxime ester reaches an excited state, and further homolysis of the nitrogen-oxygen bond occurs to form an oxygen free radical intermediate and a nitrogen free radical intermediate, which are further decarboxylated to form a heteroaryl free radical. The heteroaryl free radical attacks an olefin to form an alkyl free radical intermediate, and finally the alkyl free radical intermediate and the nitrogen free radical intermediate undergo cross-coupling to obtain a β-heteroarylethylamine derivative.

[0020] Reaction equation of the present invention:

[0021] Wherein R is a pyridine group, and R1 is a phenyl group or an alkane group.

[0022] The preparation method of oxime ester compound is:

[0023] Wherein R is a pyridine group;

[0024] 5.0 mmol of ketoxime (B) and 5.0 mmol of aromatic carboxylic acid (A) are added to 50 mL of dichloromethane solution, and 1 mmol of 4-dimethylaminopyridine and 5.0 mmol of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) are added; the mixture is degassed under a nitrogen atmosphere and stirred at room temperature until the reaction is complete as observed by TLC monitoring; the mixture is diluted with 50 mL of distilled water, the dichloromethane layer is separated, dried over anhydrous Na2SO4 and concentrated to remove the solvent, and the residue is purified by silica gel column chromatography (petroleum ether / ethyl acetate as eluent) to obtain the corresponding oxime ester compound (a).

[0025] The present invention takes β-heteroarylethylamine derivative-1 as an example, and the reaction is as follows:

[0026]

[0027] Initially, TXT is photoexcited under the irradiation of LEDs and reaches the excited state [TXT]*, which then undergoes energy transfer with the substrate oxime ester 1a to obtain 1a*. The 1a* intermediate can undergo homolytic cleavage of the carbon-oxygen bond and further decarboxylation to obtain heteroaryl radical intermediate I and nitrogen radical intermediate II. The unstable heteroaryl radical intermediate I adds to styrene 2a to obtain alkyl radical intermediate III. At this time, intermediate III can undergo cross-coupling with nitrogen radical intermediate II to obtain β-heteroarylethylamine derivative-1.

[0028] Beneficial effects of the present invention:

[0029] Compared with the existing technology, the present invention adopts a metal-free energy transfer strategy to construct aromatic tertiary amine compounds in a greener, milder, atom-economical, simpler and more efficient way, which has the following advantages:

[0030] (1) This reaction system is a difunctionalization reaction of olefins. Using an inexpensive organic photocatalyst, the energy transfer strategy can achieve the construction of complex β-heteroarylethylamine derivatives in a single step, which is convenient to operate.

[0031] (2) The reaction occurs at room temperature without the involvement of metals, and the challenging synthesis of β-heteroarylethylamine derivatives can be achieved by light irradiation. The reaction conditions are very green and mild.

[0032] (3) The oxime ester compounds, olefin compounds, and TXT used in the reaction system are all cheap and readily available chemicals, and β-heteroarylethylamine derivatives are the main products of the reaction, which reflects the atom economy of the reaction. In addition, the reaction system is economical and efficient.

[0033] (4) The reaction system has good substrate universality and can be scaled up for experiments using a one-pot method. Gram-scale synthesis can be achieved in 3-6 hours at room temperature through light irradiation, and has a good yield, reflecting the high efficiency of the reaction.

[0034] (5) The conversion of the reaction can be achieved by using a catalytic amount of an organic photosensitizer, and no metal is involved in the entire process. This brings great benefits to the post-processing of drug synthesis, and reflects the energy-saving and environmental protection of the reaction, and has potential application value.

[0035] The method of the invention is used for preparing beta-heteroarylethylamine derivatives. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 The β-heteroarylethylamine derivative-1 obtained in Example 1 1 H NMR spectrum;

[0037] Figure 2 The β-heteroarylethylamine derivative-1 obtained in Example 1 13 C NMR spectrum. DETAILED DESCRIPTION

[0038] Specific embodiment 1: This embodiment provides a method for preparing β-heteroarylethylamine derivatives by using photocatalytic energy transfer, which is specifically carried out in the following steps:

[0039] 1. adding an oxime ester compound, an olefin compound and TXT into a solvent to obtain a mixed solution;

[0040] 2. Under a nitrogen atmosphere and room temperature, the mixed solution obtained in step 1 is irradiated with an LED light source, and the solvent is removed by rotary evaporation, followed by separation and purification by thin layer chromatography. The obtained product is a β-heteroarylethylamine derivative, thereby completing the preparation;

[0041] The chemical structural formula of the oxime ester compound is:

[0042] The chemical structure of olefin compounds is:

[0043] The chemical structure of β-heteroarylethylamine derivatives is:

[0044] Wherein R is a pyridine group, and R1 is a phenyl group or an alkane group.

[0045] Specific embodiment 2: This embodiment differs from the specific embodiment 1 in that the TXT described in step 1 is a photocatalyst 9-thioxanthone, and the structural formula is:

[0046] The rest is the same as the first embodiment.

[0047] Specific embodiment 3: This embodiment differs from specific embodiment 1 or 2 in that the solvent in step 1 is ethyl acetate. Other aspects are the same as specific embodiment 1 or 2.

[0048] Specific embodiment 4: This embodiment differs from specific embodiments 1 to 3 in that the ratio of the oxime ester compound to the solvent in step 1 is 0.07-0.1 mmol:1 mL. Other aspects are the same as specific embodiments 1 to 3.

[0049] Specific embodiment 5: This embodiment differs from specific embodiments 1 to 4 in that the ratio of the olefin compound to the solvent in step 1 is 0.2-0.4 mmol:1 mL. Other steps are the same as those of specific embodiments 1 to 4.

[0050] Specific embodiment 6: This embodiment differs from specific embodiments 1 to 5 in that the ratio of TXT to solvent in step 1 is 0.5-1 mg:1 mL. Other aspects are the same as specific embodiments 1 to 5.

[0051] Specific embodiment 7: This embodiment differs from specific embodiments 1 to 6 in that the wavelength of the LED light source in step 2 is 380 to 400 nm and the power is 10 to 50 W. Other aspects are the same as specific embodiments 1 to 6.

[0052] Specific embodiment 8: This embodiment differs from specific embodiments 1 to 7 in that the light source irradiation time in step 2 is 3 to 6 hours. Other aspects are the same as specific embodiments 1 to 7.

[0053] Specific embodiment 9: This embodiment differs from specific embodiments 1 to 8 in that the solvent used in step 2 for separation and purification is a mixture of petroleum ether and ethyl acetate. Other aspects are the same as specific embodiments 1 to 8.

[0054] Specific embodiment 10: This embodiment differs from specific embodiments 1 to 9 in that the volume ratio of petroleum ether to ethyl acetate is 5:1. Other aspects are the same as those of specific embodiments 1 to 9.

[0055] The content of the present invention is not limited to the content of the above-mentioned embodiments. The combination of one or more specific embodiments can also achieve the purpose of the invention.

[0056] Example 1:

[0057] This embodiment provides a method for preparing β-heteroarylethylamine derivatives using photocatalytic energy transfer, which is specifically carried out in the following steps:

[0058] 1. Dissolve 0.2 mmol of oxime ester 1a in 2 mL of ethyl acetate, add 2 mg (5 mmol%) of photocatalyst TXT (9-thioxanthone), and then add 0.4 mmol of styrene to obtain a mixed solution;

[0059] 2. Deoxygenate the mixture by nitrogen flow for 5 minutes. Irradiate the mixed solution obtained in step 1 for 6 hours at room temperature using a 10 W LED light source with a wavelength of 390 nm while stirring with a magnetic stirrer. Monitor the progress of the reaction by TLC. Then, remove the solvent by rotary evaporation, and separate and purify the mixture by thin layer chromatography. The resulting product is a β-heteroarylethylamine derivative, thereby completing the preparation.

[0060] The structural formula of oxime ester 1a is:

[0061] The product prepared in this example was identified as β-heteroarylethylamine derivative-1 by H-NMR spectrum, C-NMR spectrum, and high-resolution mass spectrometry, and its structural formula is:

[0062]

[0063] The product purity is 99% and the yield is 68%. Its NMR data analysis is as follows: 1 H NMR(400MHz,Chloroform-d)δ8.44(d,J=4.9Hz,1H),7.60–7.56(m,2H),7.48(t,J=7.6Hz,1H),7.41(d,J=7.2Hz,2H),7.35–7.20(m,9H),7. 07(dd,J=13.5,7.3Hz,2H), 6.50(d,J=7.1Hz,2H), 4.83(dd,J=9.6,3.8Hz,1H), 3.45(dd,J=12.8,9.7Hz,1H), 3.26(dd,J=12.8,3.8Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ167.24,159.50,149.24,144.63,139.93,136.72,135.90,129.89,128.60,128 .47,128.26,128.14,127.99,127.56,127.16,126.88,124.76,121.20,67.02,48.64.HRMS(ESI)(m / z):[M+H] + calculated for C 26 H 23 N2:363.1861,found:363.1853.

[0064] Example 2:

[0065] This embodiment provides a method for preparing β-heteroarylethylamine derivatives using photocatalytic energy transfer, which is specifically carried out in the following steps:

[0066] 1. Dissolve 0.2 mmol of oxime ester 1b in 2 mL of ethyl acetate, add 2 mg (5 mmol%) of photocatalyst TXT (9-thioxanthone), and then add 0.4 mmol of styrene to obtain a mixed solution;

[0067] 2. Deoxygenate the mixture by nitrogen flow for 5 minutes. Irradiate the mixed solution obtained in step 1 for 6 hours at room temperature using a 10 W LED light source with a wavelength of 390 nm while stirring with a magnetic stirrer. Monitor the progress of the reaction by TLC. Then, remove the solvent by rotary evaporation, and separate and purify the mixture by thin layer chromatography. The resulting product is a β-heteroarylethylamine derivative, thereby completing the preparation.

[0068] The structural formula of oxime ester 1b is:

[0069] The product prepared in this example was identified as β-heteroarylethylamine derivative-2 by H-NMR spectrum, C-NMR spectrum, and high-resolution mass spectrometry, and its structural formula is:

[0070]

[0071] The product purity is 99% and the yield is 58%. Its NMR data analysis is: 1 H NMR (400MHz, Chloroform-d) δ8.35(d,J=4.6Hz,1H),7.72(d,J=8.0Hz,1H),7.62(d,J=7.0Hz,2H),7.44(d,J=7.4Hz,2H),7.38–7.26(m,8H),7.22(d,J= 7.2Hz, 1H), 6.94 (dd, J=8.0, 4.6Hz, 1H), 6.61 (d, J=7.2Hz, 2H), 5.05 (dd, J= 9.6,4.0Hz,1H),3.78(dd,J=13.1,9.6Hz,1H),3.36(dd,J=13.1,4.1Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ167.19,157.93,147.62,144.47,140.10,139.92,136.79,129.86,128.83, 128.47,128.27,128.10,127.92,127.73,127.20,126.95,122.52,65.84,47.08.HRMS(ESI)(m / z):[M+H] +calculated for C 26 H 33 BrN2:441.0966,found:441.0967.

[0072] Example 3:

[0073] This embodiment provides a method for preparing β-heteroarylethylamine derivatives using photocatalytic energy transfer, which is specifically carried out in the following steps:

[0074] 1. Dissolve 0.2 mmol of oxime ester 1c in 2 mL of ethyl acetate, add 2 mg (5 mmol%) of photocatalyst TXT (9-thioxanthone), and then add 0.4 mmol of styrene to obtain a mixed solution;

[0075] 2. Deoxygenate the mixture by nitrogen flow for 5 minutes. Irradiate the mixed solution obtained in step 1 for 6 hours at room temperature using a 10 W LED light source with a wavelength of 390 nm while stirring with a magnetic stirrer. Monitor the progress of the reaction by TLC. Then, remove the solvent by rotary evaporation, and separate and purify the mixture by thin layer chromatography. The resulting product is a β-heteroarylethylamine derivative, thereby completing the preparation.

[0076] The structural formula of oxime ester 1c is:

[0077] The product prepared in this example was identified as β-heteroarylethylamine derivative-3 by H-NMR spectrum, C-NMR spectrum, and high-resolution mass spectrometry, and its structural formula is:

[0078]

[0079] The product purity is 99% and the yield is 53%. Its NMR data analysis is as follows: 1 H NMR (400MHz, Chloroform-d) δ8.31(d,J=4.6Hz,1H),7.61(d,J=8.2Hz,2H),7.54(d,J=8.0Hz,1H),7.44(d,J=7.8Hz,2H),7.37–7.28(m,7H),7.24(d,J= 8.5Hz,2H),7.02(dd,J=7.5,4.4Hz,1H),6.62(d,J=7.4Hz,2H),5.02(dd,J= 9.5,4.0Hz,1H),3.77(dd,J=12.7,9.9Hz,1H),3.33(dd,J=13.1,3.8Hz,1H). 13C NMR(101MHz,Chloroform-d)δ167.21,156.77,147.04,144.46,139.93,136.74,132.15,130.47,129.87,128 .80,128.46,128.29,128.09,127.93,127.71,127.20,126.95,122.28,65.84,45.11.HRMS(ESI)(m / z):[M+H] + calculated for C 26 H 22 ClN2:297.1472,found:297.1471.

[0080] Example 4:

[0081] This embodiment provides a method for preparing β-heteroarylethylamine derivatives using photocatalytic energy transfer, which is specifically carried out in the following steps:

[0082] 1. Dissolve 0.2 mmol of oxime ester 1d in 2 mL of ethyl acetate, add 2 mg (5 mmol%) of photocatalyst TXT (9-thioxanthone), and then add 0.4 mmol of styrene to obtain a mixed solution;

[0083] 2. Deoxygenate the mixture by nitrogen flow for 5 minutes. Irradiate the mixed solution obtained in step 1 for 6 hours at room temperature using a 10 W LED light source with a wavelength of 390 nm while stirring with a magnetic stirrer. Monitor the progress of the reaction by TLC. Then, remove the solvent by rotary evaporation, and separate and purify the mixture by thin layer chromatography. The resulting product is a β-heteroarylethylamine derivative, thereby completing the preparation.

[0084] The structural formula of oxime ester 1d is:

[0085] The product prepared in this example was identified as β-heteroarylethylamine derivative-4 by H-NMR spectrum, C-NMR spectrum, and high-resolution mass spectrometry, and its structural formula is:

[0086]

[0087] The product purity is 99% and the yield is 34%. Its NMR data analysis is as follows: 1H NMR(400MHz,Chloroform-d)δ8.41(d,J=4.6Hz,1H),8.28(s,1H),7.62(d,J=7.9Hz,2H),7.32(p,J=8.0,7.5Hz,10H),7.26(s,2H), 7.12–7.07(m,1H),6.58(d,J=7.1Hz,2H),4.53(dd,J=8.6,4.4Hz,1H),3.23(dd,J=13.2,8.8Hz,1H),3.06(dd,J=13.3,4.4Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ167.43,150.96,147.42,143.86,139.51,137.48,136.68,134.75,130 .12,128.58,128.51,128.30,128.08,127.38,127.15,123.02,68.00,43.23.HRMS(ESI)(m / z):[M+H] + calculated for C 26 H 23 N2:363.1861,found:363.1866.

[0088] Embodiment 5:

[0089] This embodiment provides a method for preparing β-heteroarylethylamine derivatives using photocatalytic energy transfer, which is specifically carried out in the following steps:

[0090] 1. Dissolve 0.2 mmol of oxime ester 1f in 2 mL of ethyl acetate, add 2 mg (5 mmol%) of photocatalyst TXT (9-thioxanthone), and then add 0.4 mmol of styrene to obtain a mixed solution;

[0091] 2. Deoxygenate the mixture by nitrogen flow for 5 minutes. Irradiate the mixed solution obtained in step 1 for 6 hours at room temperature using a 10 W LED light source with a wavelength of 390 nm while stirring with a magnetic stirrer. Monitor the progress of the reaction by TLC. Then, remove the solvent by rotary evaporation, and separate and purify the mixture by thin layer chromatography. The resulting product is a β-heteroarylethylamine derivative, thereby completing the preparation.

[0092] The structural formula of oxime ester 1f is:

[0093] The product prepared in this example was identified as β-heteroarylethylamine derivative-5 by H-NMR spectrum, C-NMR spectrum, and high-resolution mass spectrometry, and its structural formula is:

[0094]

[0095] The product purity is 99% and the yield is 45%. Its NMR data analysis is as follows: 1 H NMR(400MHz,Chloroform-d)δ8.39(d,J=4.9Hz,2H),7.64–7.55(m,2H),7.33(p,J=7.4Hz,10H),7.25(s,1H),6.94(d,J=5 .0Hz,2H),6.59(d,J=7.1Hz,2H),4.55(dd,J=8.9,4.2Hz,1H),3.23(dd,J=12.8,9.1Hz,1H),3.04(dd,J=12.9,4.2Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ167.46,149.39,148.39,143.83,139.50,136.53,130.15,128.58,128 .56,128.36,128.28,128.09,127.52,127.19,127.09,125.31,67.59,45.55.HRMS(ESI)(m / z):[M+H] + calculated for C 26 H 23 N2:363.1861,found:363.1866.

[0096] Example 6:

[0097] This embodiment provides a method for preparing β-heteroarylethylamine derivatives using photocatalytic energy transfer, which is specifically carried out in the following steps:

[0098] 1. Dissolve 0.2 mmol of oxime ester 1a in 2 mL of ethyl acetate, add 2 mg (5 mmol%) of photocatalyst TXT (9-thioxanthone), and then add 0.4 mmol of 4-methylstyrene to obtain a mixed solution;

[0099] 2. Deoxygenate the mixture by nitrogen flow for 5 minutes. Irradiate the mixed solution obtained in step 1 for 6 hours at room temperature using a 10 W LED light source with a wavelength of 390 nm while stirring with a magnetic stirrer. Monitor the progress of the reaction by TLC. Then, remove the solvent by rotary evaporation, and separate and purify the mixture by thin layer chromatography. The resulting product is a β-heteroarylethylamine derivative, thereby completing the preparation.

[0100] The product prepared in this example was identified as β-heteroarylethylamine derivative-6 by H-NMR spectrum, C-NMR spectrum, and high-resolution mass spectrometry, and its structural formula is:

[0101]

[0102] The product purity is 99% and the yield is 67%. Its NMR data analysis is as follows: 1 H NMR(400MHz,Chloroform-d)δ8.44(d,J=4.8Hz,1H),7.57(d,J=7.7Hz,2H),7.48(t,J=7.6Hz,1H),7.35–7.24(m,8H),7.09–7.02(m,2H),6.85 (d,J=8.4Hz,2H),6.51(d,J=7.3Hz,2H),4.78(dd,J=9.5,3.8Hz,1H),3.78(s,3H),3.43(dd,J=12.7,9.6Hz,1H),3.23(dd,J=12.7,3.9Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ166.99,159.54,158.47,149.17,139.92,136.78,136.74,135.91,129.86,128 .59,128.25,128.12,127.97,127.56,124.74,121.17,113.82,66.38,55.29,48.63.HRMS(ESI)(m / z):[M+H] + calculated for C 27 H 25 N2:377.2018,found:377.2009.

[0103] Embodiment seven:

[0104] This embodiment provides a method for preparing β-heteroarylethylamine derivatives using photocatalytic energy transfer, which is specifically carried out in the following steps:

[0105] 1. Dissolve 0.2 mmol of oxime ester 1a in 2 mL of ethyl acetate, add 2 mg (5 mmol%) of photocatalyst TXT (9-thioxanthone), and then add 0.4 mmol of 4-methoxystyrene to obtain a mixed solution;

[0106] 2. Deoxygenate the mixture by nitrogen flow for 5 minutes. Irradiate the mixed solution obtained in step 1 for 6 hours at room temperature using a 10 W LED light source with a wavelength of 390 nm while stirring with a magnetic stirrer. Monitor the progress of the reaction by TLC. Then, remove the solvent by rotary evaporation, and separate and purify the mixture by thin layer chromatography. The resulting product is a β-heteroarylethylamine derivative, thereby completing the preparation.

[0107] The product prepared in this example was identified as β-heteroarylethylamine derivative-7 by H-NMR spectrum, C-NMR spectrum, and high-resolution mass spectrometry, and its structural formula is:

[0108]

[0109] The product purity is 99% and the yield is 65%. Its NMR data analysis is: 1 H NMR(400MHz,Chloroform-d)δ8.44(d,J=4.1Hz,1H),7.58(d,J=6.9Hz,2H),7.49(t,J=7.6Hz,1H),7.29(dd,J=15.6,8.2Hz,8H),7.13–7 .04(m,4H),6.50(d,J=7.1Hz,2H),4.80(dd,J=9.7,3.7Hz,1H),3.45(dd,J=12.8,9.7Hz,1H),3.24(dd,J=12.8,3.7Hz,1H),2.33(s,3H). 13 C NMR(101MHz,Chloroform-d)δ167.04,159.58,149.19,141.63,139.95,136.73,136.38,135.89,129.82,129 .15,128.58,128.22,127.95,127.57,127.00,124.75,121.16,66.74,48.63,21.21.HRMS(ESI)(m / z):[M+H] + calculated for C 27 H 25 O:393.1967,found:393.1964.

[0110] Embodiment 8:

[0111] This embodiment provides a method for preparing β-heteroarylethylamine derivatives using photocatalytic energy transfer, which is specifically carried out in the following steps:

[0112] 1. Dissolve 0.2 mmol of oxime ester 1a in 2 mL of ethyl acetate, add 2 mg (5 mmol%) of photocatalyst TXT (9-thioxanthone), and then add 0.4 mmol of 4-chlorostyrene to obtain a mixed solution;

[0113] 2. Deoxygenate the mixture by nitrogen flow for 5 minutes. Irradiate the mixed solution obtained in step 1 for 6 hours at room temperature using a 10 W LED light source with a wavelength of 390 nm while stirring with a magnetic stirrer. Monitor the progress of the reaction by TLC. Then, remove the solvent by rotary evaporation, and separate and purify the mixture by thin layer chromatography. The resulting product is a β-heteroarylethylamine derivative, thereby completing the preparation.

[0114] The product prepared in this example was identified as β-heteroarylethylamine derivative-8 by H-NMR spectrum, C-NMR spectrum, and high-resolution mass spectrometry, and its structural formula is:

[0115]

[0116] The product purity is 99% and the yield is 78%. Its NMR data analysis is as follows: 1 H NMR (400MHz, Chloroform-d) δ8.43(d,J=3.8Hz,1H),7.58(d,J=6.9Hz,2H),7.48(t,J=7.6Hz,1H),7.36–7.24(m,10H),7.06(dd,J =7.5, 4.0Hz, 2H), 6.50 (d, J = 7.0Hz, 2H), 4.80 (dd, J = 9.4, 4.0Hz, 1H), 3.40 (dd, J = 12.8, 9.5Hz, 1H), 3.21 (dd, J = 12.8, 4.0Hz, 1H). 13 C NMR(101MHz,Chloroform-d)δ167.68,159.09,149.27,143.11,139.72,136.57,135.98,132.47,130.06, 128.59,128.51,128.38,128.22,128.04,127.45,124.71,121.31,66.33,48.55.HRMS(ESI)(m / z):[M+H] + calculated for C 26 H 22 ClN2:397.1472,found:397.1468.

[0117] Embodiment 9:

[0118] This embodiment provides a method for preparing β-heteroarylethylamine derivatives using photocatalytic energy transfer, which is specifically carried out in the following steps:

[0119] 1. Dissolve 0.2 mmol of oxime ester 1a in 2 mL of ethyl acetate, add 2 mg (5 mmol%) of photocatalyst TXT (9-thioxanthone), and then add 0.8 mmol of n-octene to obtain a mixed solution;

[0120] 2. Deoxygenate the mixture by nitrogen flow for 5 minutes. Irradiate the mixed solution obtained in step 1 for 6 hours at room temperature using a 10 W LED light source with a wavelength of 390 nm while stirring with a magnetic stirrer. Monitor the progress of the reaction by TLC. Then, remove the solvent by rotary evaporation, and separate and purify the mixture by thin layer chromatography. The resulting product is a β-heteroarylethylamine derivative, thereby completing the preparation.

[0121] The product prepared in this example was identified as β-heteroarylethylamine derivative-9 by H-NMR spectrum, C-NMR spectrum, and high-resolution mass spectrometry, and its structural formula is:

[0122]

[0123] The product purity is 99% and the yield is 46%. Its NMR data analysis is as follows: 1 H NMR(400MHz,Chloroform-d)δ8.44(d,J=4.7Hz,1H),7.54(d,J=6.7Hz,2H),7.47(d,J=7.6Hz,1H),7.33–7.23(m,6H),7.06(t,J=7.4H z,2H),6.47(d,J=6.9Hz,2H),3.69(tt,J=8.5,4.5Hz,1H),3.10–2.99(m,2H),1.76–1.60(m,2H),1.22(s,8H),0.85(t,J=6.8Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ166.97,160.19,149.19,140.17,137.12,135.87,129.65,128.41,128.03,128.01, 127.93,127.58,124.60,121.03,63.02,45.83,37.09,31.88,29.52,26.58,22.70,14.16.HRMS(ESI)(m / z):[M+H] + calculated for C 26 H 31 N2:371.2487,found:371.2489.

[0124] Embodiment 10:

[0125] Gram-scale reaction

[0126] This embodiment provides a method for preparing β-heteroarylethylamine derivatives using photocatalytic energy transfer, which is specifically carried out in the following steps:

[0127] 1. Dissolve 6 mmol of oxime ester 1a and 12 mmol of styrene in 60 mL of ethyl acetate, and then add 60 mg of photocatalyst TXT (9-thioxanthone) to obtain a mixed solution;

[0128] 2. Deoxygenate the mixture by nitrogen flow for 15 minutes. Irradiate the mixed solution obtained in step 1 for 6 hours at room temperature using a 50 W LED light source with a wavelength of 390 nm while stirring with a magnetic stirrer. Monitor the progress of the reaction by TLC. Then, remove the solvent by rotary evaporation, and separate and purify the mixture by thin layer chromatography. The resulting product is a β-heteroarylethylamine derivative, thereby completing the preparation.

[0129] The product prepared in this example was identified as β-heteroarylethylamine derivative-1 by H-NMR spectrum, C-NMR spectrum, and high-resolution mass spectrometry, and its structural formula is:

[0130]

[0131] The purity is 99% and the yield is 68%. The NMR data analysis is as follows: 1 H NMR(400MHz,Chloroform-d)δ8.44(d,J=4.9Hz,1H),7.60–7.56(m,2H),7.48(t,J=7.6Hz,1H),7.41(d,J=7.2Hz,2H),7.35–7.20(m,9H),7. 07(dd,J=13.5,7.3Hz,2H), 6.50(d,J=7.1Hz,2H), 4.83(dd,J=9.6,3.8Hz,1H), 3.45(dd,J=12.8,9.7Hz,1H), 3.26(dd,J=12.8,3.8Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ167.24,159.50,149.24,144.63,139.93,136.72,135.90,129.89,128.60,128 .47,128.26,128.14,127.99,127.56,127.16,126.88,124.76,121.20,67.02,48.64.HRMS(ESI)(m / z):[M+H] + calculated for C 26 H 23 N2:363.1861,found:363.1853.

[0132] The embodiment described above is only a preferred solution of the present invention and does not limit the present invention in any form. Other variations and modifications are possible without exceeding the technical solution described in the claims.

Claims

1. A method for preparing β-heteroarylethylamine derivatives by photocatalytic energy transfer, characterized in that The method is specifically carried out in the following steps:

1. Add oxime ester compounds, olefin compounds and TXT to a solvent to obtain a mixed solution; TXT is a photocatalyst 9-thioxanthone, and its structural formula is: ; 2. Under a nitrogen atmosphere and room temperature, the mixed solution obtained in step 1 is irradiated with an LED light source, and the solvent is removed by rotary evaporation, followed by separation and purification by thin layer chromatography. The obtained product is a β-heteroarylethylamine derivative, thereby completing the preparation; The chemical structural formula of the oxime ester compound is: , and selected from 、 、 or ; The chemical structure of olefin compounds is: , and is selected from styrene, 4-methylstyrene or 4-chlorostyrene; The chemical structure of β-heteroarylethylamine derivatives is: , and selected from 、 、 、 、 or .

2. The method for preparing β-heteroarylethylamine derivatives by utilizing photocatalytic energy transfer according to claim 1, characterized in that The solvent in step 1 is ethyl acetate.

3. The method for preparing β-heteroarylethylamine derivatives by utilizing photocatalytic energy transfer according to claim 1, characterized in that The ratio of the oxime ester compound to the solvent in step 1 is 0.07-0.1 mmol:1 mL.

4. The method for preparing β-heteroarylethylamine derivatives by utilizing photocatalytic energy transfer according to claim 1, characterized in that The ratio of the olefin compound to the solvent in step 1 is 0.2-0.4 mmol:1 mL.

5. The method for preparing β-heteroarylethylamine derivatives by utilizing photocatalytic energy transfer according to claim 1, characterized in that The ratio of TXT to solvent in step 1 is 0.5-1 mg:1 mL.

6. The method for preparing β-heteroarylethylamine derivatives by utilizing photocatalytic energy transfer according to claim 1, characterized in that The wavelength of the LED light source in step 2 is 380-400 nm, and the power is 10-50 W.

7. The method for preparing β-heteroarylethylamine derivatives by utilizing photocatalytic energy transfer according to claim 1, characterized in that The light source irradiation time in step 2 is 3 to 6 hours.

8. The method for preparing β-heteroarylethylamine derivatives by utilizing photocatalytic energy transfer according to claim 1, characterized in that The solvent used in step 2 for separation and purification is a mixture of petroleum ether and ethyl acetate.

9. The method for preparing β-heteroarylethylamine derivatives by utilizing photocatalytic energy transfer according to claim 8, characterized in that The volume ratio of petroleum ether to ethyl acetate was 5:1.

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