Synthetic method of gamma-aminoketone
By using materials such as olefins, aniline, acyl fluoride, photocatalysts and azacyclic carbene for visible light excitation reactions at room temperature, the problem of insufficient γ-amino ketone synthesis is solved, and efficient and applicable γ-amino ketone synthesis is achieved. Improves the potential of drug discovery and drug synthesis.
Patent Information
- Application Number
- CN202411314297.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-20
- Publication Date
- 2024-12-27
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
The synthesis methods of γ-amino ketones in the prior art are relatively limited, and there is a lack of efficient synthesis methods, which affects the progress of drug discovery and drug synthesis.
The reaction was carried out under visible light excitation conditions using olefins, aniline, acyl fluoride, photocatalysts, azolid carbene and alkali at room temperature, and the reaction was carried out under visible light excitation conditions. The combination of specific solvents and photocatalysts was achieved to achieve efficient synthesis of γ-amino ketones.
It provides a γ-amino ketone synthesis method with simple reaction conditions and wide substrate applicability, which improves yield and reaction efficiency, and is suitable for the preparation of a variety of γ-amino ketones.
Smart Images
Figure SMS_1 
Figure SMS_2 
Figure SMS_3
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing gamma-aminoketone. Background Art
[0002] Aminoketones and their derivatives are present in many active pharmaceutical ingredients, fine chemicals, agrochemicals, polymers, dyes, pigments, emulsifiers and plasticizers, and other chemicals. Due to the challenges and practicality of their synthesis, the development of new and efficient synthesis methods has long been a hot topic for synthetic chemists. γ-Aminoketone is a commonly used chiral building block for the synthesis of chiral and achiral amino compounds. In the past, the methods for synthesizing aminoketones have always focused more on the synthesis of α-aminoketones and β-aminoketones, but there have been few reports on the synthesis of γ-aminoketones. Based on this, the development of efficient methods for the synthesis of γ-aminoketones is of great significance in drug discovery and drug synthesis. Summary of the invention
[0003] The purpose of the present invention is to overcome the defects of the existing preparation technology and provide a method for synthesizing γ-aminoketone with simple reaction conditions and wide substrate applicability.
[0004] The technical scheme of the present invention is: olefin, aniline, acyl fluoride, photocatalyst, nitrogen heterocyclic carbene, base are added into a reaction tube, solvent is added, and γ-amino ketone is obtained under room temperature and visible light excitation conditions, and the reaction formula is as follows:
[0005]
[0006] (1)R 1 Selected from ester, chloro, naphthalene, phenyl, cyano, pyridine;
[0007] (2)R 2 Selected from phenyl, thiophene;
[0008] (3)R 3 Selected from methyl, chloro, ester, cyano;
[0009] (4)R 4 Selected from ethyl, phenyl, benzyl;
[0010] (5)R 5 Selected from methyl, tert-butyl, phenyl, chloro, methoxy;
[0011] (6) The base used is selected from cesium carbonate and potassium bicarbonate;
[0012] (7) The solvent used is selected from acetonitrile;
[0013] (8) The photocatalyst used is selected from (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate;
[0014] (9) The nitrogen heterocyclic carbene used is selected from 3-ethylbenzo[d]thiazol-3-ium bromide;
[0015] (10) The temperature used is selected from 25°C and maintained for 4 hours;
[0016] (11) The visible light used is selected from 12W 460nm LED blue light, and the duration is 4 hours. BRIEF DESCRIPTION OF THE DRAWINGS
[0017] Figure 1 The synthesis conditions of γ-aminoketone;
[0018] Figure 2 is the preparation reaction formula of compound 4aa;
[0019] Figure 3 is the preparation reaction formula of compound 4ab;
[0020] Figure 4 is the preparation reaction formula of compound 4ac;
[0021] Figure 5 is the preparation reaction formula of compound 4ad;
[0022] Figure 6 is the preparation reaction formula of compound 4ae;
[0023] Figure 7 is the reaction formula for preparing compound 4af;
[0024] Figure 8 is the preparation reaction formula of compound 4ag;
[0025] Fig. 9 is the preparation reaction formula of compound 4ah;
[0026] Fig.10 is the preparation reaction formula of compound 4ai;
[0027] Fig.11 is the preparation reaction formula of compound 4aj;
[0028] Fig.12 is the preparation reaction formula of compound 4ba;
[0029] Fig.13 is the preparation reaction formula of compound 4bb;
[0030] Fig.14 is the preparation reaction formula of compound 4bc;
[0031] Fig.15 is the preparation reaction formula of compound 4bd;
[0032] Fig.16 is the preparation reaction formula of compound 4be;
[0033] Fig.17 is the preparation reaction formula of compound 4bf;
[0034] Fig.18 is the preparation reaction formula of compound 4bg;
[0035] Fig.19 is the reaction formula for the preparation of compound 4ca;
[0036] Fig. 20 is the preparation reaction formula of compound 4cb;
[0037] Fig.21 is the reaction formula for the preparation of compound 4cc;
[0038] Fig. 22 is the preparation reaction formula of compound 4cd;
[0039] Fig.23 This is the reaction formula for the preparation of compound 4ce. DETAILED DESCRIPTION
[0040] The present invention is further described below through specific embodiments, but this should not be understood as the scope of the above subject matter of the present invention being limited to the following embodiments, and all technologies implemented based on the above content of the present invention belong to the scope of the present invention.
[0041] Implementation Case 1: Using 4-vinylbenzoic acid methyl ester, N,N-dimethylaniline and benzoyl fluoride as raw materials (reaction formula 1)
[0042]
[0043] Under argon atmosphere, olefin substrate 1a (0.1mmol, 16.2mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and N,N-dimethylaniline (0.25mmol, 32μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W460nmLED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=20:1-10:1) to obtain the target product 4aa.
[0044] The product testing data are as follows:
[0045] Yellow oil, yield 80%.
[0046] 1 H NMR (400MHz, CDCl3) δ7.88(d,J=8.4Hz,2H),7.81(d,J=7.2Hz,2H),7.40(t,J=7.2Hz,1H),7.29(d,J=7.6Hz,4H),7.10(dd,J=8.8,7.2Hz, 2H),6.61–6.56(m,3H),4.57(dd,J=8.0,6.4Hz,1H),3.79(s,3H),3.29–3.16(m,2H),2.78(s,3H),2.52–2.42(m,1H),2.03–1.96(m,1H).
[0047] 13 C NMR (100MHz, CDCl3) δ198.7,166.8,149.3,144.5,136.4,133.2,130.3,129. 22,129.16,128.7,128.6,128.3,116.6,112.6,52.1,51.0,50.7,38.4,31.1.
[0048] Implementation Case 2 Using 2-vinylnaphthalene, N,N-dimethylaniline and benzoyl fluoride as raw materials (Reaction Formula 2)
[0049]
[0050] Under argon atmosphere, olefin substrate 1b (0.1mmol, 15.4mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and N,N-dimethylaniline (0.25mmol, 32μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature under 12W 460nm LED blue light and stirred until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=40:1-20:1) to obtain the target product 4ab.
[0051] The product testing data are as follows:
[0052] Yellow oil, yield 40%.
[0053] 1H NMR (400MHz, CDCl3): δ7.97–7.94(m,2H),7.80–7.75(m,3H),7.73(s,1H),7.47–7.41(m,4H),7.36–7.32(m,2H),7.19–7.15(m,2 H),6.68–6.66(m,3H),7.74–7.77(dd,J=8.0,6.4Hz,1H),3.44–3.28(m,2H),2.88(s,3H),2.66–2.56(m,1H),2.21–2.12(m,1H).
[0054] 13 C NMR (100MHz, CDCl3): δ199.3,149.4,136.80,136.6,133.6,133.0,132.5,129.2,128.9,128 .8,128.6,127.8,127.7,127.2,126.3,126.2,126.0,116.4,112.6,51.2,50.8,38.3,31.1.
[0055] Implementation Case 3 Using 4-vinylbiphenyl, N,N-dimethylaniline and benzoyl fluoride as raw materials (Reaction Formula 3)
[0056]
[0057] Under argon atmosphere, olefin substrate 1c (0.1mmol, 18.0mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and N,N-dimethylaniline (0.25mmol, 32μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W460nmLED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=40:1-20:1) to obtain the target product 4ac.
[0058] The product testing data are as follows:
[0059] White solid, yield 60%.
[0060] 1HNMR (400MHz, CDCl3): δ7.96(d,J=7.2Hz,2H),7.55–7.52(m,4H),7.48(d,J=7.2Hz,1H),7.43–7.36(m,6H),7.32(t,J=7.6Hz,1H),7.19(dd, J=8.8,7.6Hz,2H),6.67(t,J=4.4Hz,3H),4.64(dd,J=8.0,6.4Hz,1H),3.42–3.29(m,2H),2.90(s,3H),2.61–2.52(m,1H),2.16–2.07(m,1H).
[0061] 13 C NMR (100MHz, CDCl3): δ199.3,149.4,140.6,140.1,138.3,136.6,133.0,129.2,128. 78,128.75,128.7,128.6,127.7,127.4,127.0,116.4,112.5,50.8,50.7,38.3,31.1.
[0062] Implementation Case 4 Using 4-chlorostyrene, N,N-dimethylaniline and benzoyl fluoride as raw materials (Reaction Formula 4)
[0063]
[0064] Under argon atmosphere, olefin substrate 1d (0.1mmol, 13.9mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and then N,N-dimethylaniline (0.25mmol, 32μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature under 12W 460nm LED blue light and stirred until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=40:1-20:1) to obtain the target product 4ad.
[0065] The product testing data are as follows:
[0066] Yellow oil, yield 59%.
[0067] 1H NMR (400MHz, CDCl3): δ7.88(d,J=8Hz,),7.48(t,J=8.4Hz,1H),7.40(t,J=7.6Hz,2H),7.27-7.21(m,4H),7.20–7.16(m, 2H),6.69–6.64(m,3H),4.57(dd,J=8.4,6.4Hz),3.37–3.23(m,2H),2.86(s,3H),2.55–2.46(m,1H),2.08–1.99(m,1H).
[0068] 13 C NMR (100MHz, CDCl3): δ199.0,149.3,137.8,136.4,133.1,129.6,129.2,128.65,128.63,116.6,112.6,50.7,50.3,38.4,31.2.
[0069] Implementation Case 5 Using 4-cyanostyrene, N,N-dimethylaniline and benzoyl fluoride as raw materials (Reaction Formula 5)
[0070]
[0071] Under argon atmosphere, olefin substrate 1e (0.1mmol, 13.0mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and N,N-dimethylaniline (0.25mmol, 32μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W460nmLED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=15:1-5:1) to obtain the target product 4ae.
[0072] The product testing data are as follows:
[0073] Yellow oil, yield 78%.
[0074] 1HNMR (400MHz, CDCl3): δ7.86(d,J=7.2Hz,2H),7.58(d,J=8.4Hz,2H),7.53–7.49(m,1H),7.43–7.37(m,4H),7.18(dd,J=8.8,7.2Hz,2H),6 .71–6.68(m,1H),6.64(d,J=7.6Hz,2H),4.67(dd,J=8.4,6Hz,1H),3.37–3.26(m,2H),2.85(s,3H),2.60–2.53(m,1H),2.08–2.02(m,1H).
[0075] 13 C NMR (100MHz, CDCl3): δ198.3,149.2,144.7,136.1,133.5,132.8,129.2,129.1,128.8,128.6,118.6,116.8,112.7,111.2,50.8,50.6,38.4,31.4.
[0076] Implementation Case 6 Using 2-vinylpyridine, N,N-dimethylaniline and benzoyl fluoride as raw materials (Reaction Formula 6)
[0077]
[0078]
[0079] Under argon atmosphere, olefin substrate 1f (0.1mmol, 11.0mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and N,N-dimethylaniline (0.25mmol, 32μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W460nmLED blue light until the raw materials disappeared. After the reaction, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=15:1-5:1) to obtain the target product 4af.
[0080] The product testing data are as follows:
[0081] Yellow oil, yield 53%.
[0082] 1HNMR (400MHz, CDCl3): δ8.54(dd,J=4,1.2Hz,1H),8.00(d,J=7.2Hz,2H),7.58(t,J=7.6Hz,1H),7.46(t,J=7.2Hz,1H),7.36(t,J=7.6Hz,2H),7.24 (s,1H),7.18–7.10(m,3H),6.66–6.62(m,3H),4.87(dd,J=8.4,6.4Hz,1H ),3.38–3.29(m,2H),2.87(s,3H),2.59–2.54(m,1H),2.17–2.12(m,1H).
[0083] 13 C NMR (100MHz, CDCl3): δ198.6,159.3,149.7,149.2,137.0,136.6,133.1,129.2,129.0,128.6,122.3,122.1,116.3,112.4,54.1,50.8,38.3,30.1.
[0084] Implementation Case 7 Using 1,1-phenylethylene, N,N-dimethylaniline and benzoyl fluoride as raw materials (Reaction Formula 7)
[0085]
[0086] Under argon environment, 1g (0.1mmol, 18.0mg) of olefin substrate, photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL of acetonitrile was added, and N,N-dimethylaniline (0.25mmol, 32μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W460nmLED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=15:1-5:1) to obtain the target product 4ag.
[0087] The product testing data are as follows:
[0088] Yellow oil, yield 69%.
[0089] 1HNMR (400MHz, CDCl3): δ7.40(dd,J=8.4,1.2Hz,2H),7.35–7.32(m,4H),7.28–7.24(m,5H),7.21–7.16(m,2H),7.12(t,J=8.0Hz,2 H),7.02(dd,J=8.8,7.2Hz,2H),6.52(t,J=7.2Hz,1H),6.32(d,J=7.6Hz,2H),3.02–2.98(m,2H),2.66(s,3H),2.53–2.49(m,2H).
[0090] 13 C NMR (100MHz, CDCl3): δ201.2,148.8,141.6,137.3,131.8,130.0,129.2,129.1,128.5,127.9,127.1,115.7,111.8,63.4,49.2,37.7.
[0091] Implementation Case 8 Using 2-(1-phenylvinyl)thiophene, N,N-dimethylaniline and benzoyl fluoride as raw materials (Reaction Formula 8)
[0092]
[0093] Under argon atmosphere, olefin substrate 1h (0.1mmol, 18.6mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and N,N-dimethylaniline (0.25mmol, 32μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W460nmLED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=15:1-5:1) to obtain the target product 4ah.
[0094] The product testing data are as follows:
[0095] White solid, yield 73%.
[0096] 1HNMR (400MHz, CDCl3): δ7.53(d,J=6.8Hz,2H),7.40(d,J=6.8Hz,2H),7.34–7.21(m,4H),7.19–7.14(m,3H),6.98(dd,J= 8.8,7.2Hz,2H),6.88–6.85(m,2H),6.51(t,J=7.2Hz,1H),6.23(d,J=8.0Hz,2H),3.16–2.97(m,2H),2.68–2.54(m,5H).
[0097] 13 C NMR (100MHz, CDCl3): δ199.4,148.7,145.7,142.3,136.6,132.1,130.1,129.1,128. 9,128.1,127.7,127.65,127.61,126.4,125.4,115.9,111.8,60.9,48.8,38.0,37.8.
[0098] Implementation Case 9
[0099] Using 4-ester styrene, N,N-dimethylaniline and benzoyl fluoride as raw materials (reaction formula 9)
[0100]
[0101] Under argon atmosphere, olefin substrate 1i (0.1mmol, 28.4mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and then N,N-dimethylaniline (0.25mmol, 32μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W 460nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=15:1-5:1) to obtain the target product 4ai.
[0102] The product testing data are as follows:
[0103] Yellow oil, yield 83%.
[0104] 1H NMR (400MHz, CDCl3): δ7.90(d,J=8.4Hz,2H),7.90(d,J=7.2Hz,2H),7.48(t,J=7.2Hz,1H),7.37(t,J=8.4Hz,4H) ,7.17(dd,J=8.8,7.2Hz,2H),6.69–6.44(m,3H),4.67(dd,J=8.0,6.0Hz,1H),4.58(s,1H),3.38–3.27(m,2H),2. 87(s,3H),2.60–2.53(m,1H),2.12–2.03(m,1H),1.92–1,85(m,1H),1.79–1.73(m,2H),1.64(d,J=10.4Hz,1H),1 ,54–1,49(m,1H),1.23(dd,J=10.8,7.2Hz,2H),1,18–1.13(m,4H),1.08(d,J=4.8Hz,3H),0.81(d,J=3.6Hz,3H).
[0105] 13 C NMR (100MHz, CDCl3): δ198.7,166.5,149.3,144.4,136.4,133.2,130.3,129.7,129.2,128.7,128.6,1 28.3,116.6,112.6,86.8,51.0,50.7,48.6,48.4,41.5,39.8,38.4,31.2,29.8,26.7,25.9,20.3,19.5.
[0106] Implementation Case 10
[0107] Using 4-ester styrene, N,N-dimethylaniline and benzoyl fluoride as raw materials (reaction formula 10)
[0108]
[0109] Under argon environment, olefin substrate 1j (0.1mmol, 29.8mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and N,N-dimethylaniline (0.25mmol, 32μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W460nmLED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=15:1-5:1) to obtain the target product 4aj.
[0110] The product testing data are as follows:
[0111] Colorless oil, yield 83%.
[0112] 1 HNMR (400MHz, CDCl3): δ7.98(d,J=8.0Hz,2H),7.87(d,J=7.2Hz,2H),7.48–7.44(m ,1H),7.37–7.33(m,4H),7.16(dd,J=8.8,7.2Hz,2H),7.00–6.94(m,2H),6.84(d,J= 8.0Hz,1H),6.68–6.63(m,3H),5.25(s,2H),4.65(dd,J=8.0,6.0Hz,1H),3.87(d,J =3.2Hz,6H),3.36–3.23(m,2H),2.85(s,3H),2.57–2.51(m,1H),2.08–2.03(m,1H).
[0113] 13 C NMR (100MHz, CDCl3): δ198.7,166.1,149.3,149.2,149.1,144.7,136.4,133.2,130.4,129.2,128.9 ,128.7,128.6,128.5,128.3,121.3,116.6,112.6,111.9,111.1,66.9,56.0,51.0,50.7,38.4,31.1.
[0114] Example 11 Using 4-vinylbenzoic acid methyl ester, N, N-4-trimethylaniline and benzoyl fluoride as raw materials (reaction formula 11)
[0115]
[0116] Under argon atmosphere, olefin substrate 1a (0.1mmol, 16.2mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and N,N-4-trimethylaniline 2b (0.25mmol, 36μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W 460nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=20:1-10:1) to obtain the target product 4ba.
[0117] The product testing data are as follows:
[0118] Yellow oil, yield 65%.
[0119] 1 H NMR (400MHz, CDCl3): δ7.96(d,J=8.4Hz,2H),7.89(d,J=7.2Hz,2H),7.48(t,J=7.2Hz,1H),7.38–7.35(m,4H),6.99(d,J=8.0Hz,2H),6.59(d ,J=8.8Hz,2H),4.67(dd,J=8.06.4Hz,1H),3.88(s,3H),3.33–3.23(m,2H),2.83(s,3H),2.58–2.49(m,1H),2.23(s,3H),2.10–2.01(m,1H).
[0120] 13 C NMR (100MHz, CDCl3): δ198.8,166.8,147.4,144.6,136.4,133.1,130.3,129.7,1 29.1,128.65,128.60,128.3,126.0,113.2,52.1,51.04,50.98,38.6,31.0,20.2.
[0121] Example 12 Using 4-vinylbenzoic acid methyl ester, 4-dimethylaminobenzoic acid methyl ester and benzoyl fluoride as raw materials (reaction formula 12)
[0122]
[0123] Under argon atmosphere, olefin substrate 1a (0.1mmol, 16.2mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and then 4-dimethylaminobenzoic acid methyl ester 2c (0.25mmol, 40μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W 460nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=10:1-5:1) to obtain the target product 4bb.
[0124] The product testing data are as follows:
[0125] Yellow oil, yield 83%.
[0126] 1 H NMR (400MHz, CDCl3): δ7.96(d,J=8.4Hz,2H),7.88(d,J=6.8Hz,2H),7.84(d,J=9.2Hz,2H),7.47(t,J=7.6Hz,1H),7.36(d,J=8.4Hz,4H),6.57 (d,J=9.2Hz,2H),4.61(dd,J=8.0,6.0Hz,1H),3.85(d,J=12.8Hz,6H),3.46–3.30(m,2H),2.93(s,3H),2.59–2.50(m,1H),2.09–2.04(m,1H).
[0127] 13 C NMR (100MHz, CDCl3): δ198.4,167.4,166.6,152.2,144.2,136.1,133.3,131.4,130 .4,129.3,128.68,128.7,128.2,117.1,110.8,52.1,51.5,51.0,50.3,38.2,31.0.
[0128] Example 13 Using 4-vinylbenzoic acid methyl ester, 4-dimethylaminobenzonitrile and benzoyl fluoride as raw materials (reaction formula 13)
[0129]
[0130] Under argon atmosphere, olefin substrate 1a (0.1mmol, 16.2mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and then 4-chloro-N,N-dimethylaniline 2e (0.25mmol, 28μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W 460nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=10:1-5:1) to obtain the target product 4bc.
[0131] The product testing data are as follows:
[0132] Yellow oil, yield 67%.
[0133] 1 H NMR (400MHz, CDCl3): δ7.98(d,J=8.0Hz,2H),7.88(d,J=7.6Hz,2H),7.50(t,J=7.2Hz,1H),7.40–7.36(m,6H),6.59(d,J=8 .8Hz,2H),4.60(dd,J=8.8,5.6Hz,1H),3.88(s,3H),3.46–3.30(m,2H),2.95(s,3H),2.58–2.52(m,1H),2.09–2.03(m,1H).
[0134] 13 C NMR (100MHz, CDCl3): δ198.3,166.6,151.4,144.1,136.1,133.6,133.5,130.5 ,129.4,128.7,128.7,128.1,120.6,111.5,97.5,52.2,51.0,50.2,38.1,30.9.
[0135] Example 14 Using 4-vinylbenzoic acid methyl ester, 4-chloro-N,N-dimethylaniline and benzoyl fluoride as raw materials (reaction formula 14)
[0136]
[0137] Under argon atmosphere, olefin substrate 1a (0.1mmol, 16.2mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and then 4-chloro-N,N-dimethylaniline 2e (0.25mmol, 37μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W 460nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=20:1-10:1) to obtain the target product 4bd.
[0138] The product testing data are as follows:
[0139] Yellow oil, yield 74%.
[0140] 1 H NMR (400MHz, CDCl3): δ7.97(d,J=8.0Hz,2H),7.90(d,J=8.0Hz,2H),7.51–7.46(m,1H),7.39–7.35(m,4H),7.10(d,J=8.8Hz,2H),6. 50(d,J=8.8Hz,2H),4.63(dd,J=8.4,6.0Hz,1H),3.88(s,3H),3.37–3.22(m,2H),2.84(s,3H),2.56–2.49(m,1H),2.08–2.00(m,1H).
[0141] 13 C NMR (100MHz, CDCl3): δ198.5,166.7,147.8,144.4,136.3,133.3,130.4,129 .2,129.0,128.7,128.6,128.2,121.3,113.6,52.1,51.0,50.8,38.4,30.9.
[0142] Example 15 Using 4-vinylbenzoic acid methyl ester, N-ethyl-N-methylaniline and benzoyl fluoride as raw materials (reaction formula 15)
[0143]
[0144] Under argon atmosphere, olefin substrate 1a (0.1mmol, 16.2mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and then N-ethyl-N-methylaniline 2f (0.25mmol, 36μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W 460nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=20:1-10:1) to obtain the target product 4be.
[0145] The product testing data are as follows:
[0146] Yellow oil, yield 70%.
[0147] 1 H NMR (400MHz, CDCl3): δ7.97(d,J=8.4Hz,2H),7.91(d,J=7.2Hz,2H),7.50(t,J=7.2Hz,1H),7.38(t,J=8.4Hz,4H),7.18(dd,J=8.8,7.6Hz,2H) ,6.68–6.64(m,3H),4.67(dd,J=8.4,6.4Hz,1H),3.88(s,3H),3.30–3. 23(m,4H),2.60–2.54(m,1H),2.10–2.05(m,1H),1.09(t,J=7.2Hz,3H).
[0148] 13 C NMR (100MHz, CDCl3): δ198.7,166.8,147.8,144.6,136.4,133.2,130.3,129.3 ,129.1,128.7,128.6,128.3,116.1,112.6,52.1,51.1,48.2,45.2,31.8,12.2.
[0149] Example 16 Using 4-vinylbenzoic acid methyl ester, N-methyldiphenylamine and benzoyl fluoride as raw materials (reaction formula 16)
[0150]
[0151] Under argon environment, olefin substrate 1a (0.1mmol, 16.2mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and then N-methyldiphenylamine 2g (0.25mmol, 44μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W 460nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=20:1-10:1) to obtain the target product 4bf.
[0152] The product testing data are as follows:
[0153] Yellow oil, yield 78%.
[0154] 1 HNMR (400MHz, CDCl3): δ7.93(d,J=8.4Hz,2H),7.84(d,J=6.8Hz,2H),7.49-7.45(m,1H),7.35(t,J=8.0Hz,2H),7.29(d,J=8.4Hz,2H),7.22( dd,J=8.8,7.2Hz,4H),6.97-6.91(m,6H),4.68(dd,J=8.0,6.4Hz,1H),3.87(s,3H),3.80-3.65(m,2H),2.67-2.58(m,1H),2.20-2.11(m,1H).
[0155] 13 C NMR (100MHz, CDCl3): δ199.8,166.7,147.9,144.4,136.3,133.2,130.3,129.4,129.2,128.7,128.6,128.3,121.5,121.0,52.1,51.1,50.1,31.9.
[0156] Implementation Example 17 Using 4-vinylbenzoic acid methyl ester, N-methyl-N-benzylaniline and benzoyl fluoride as raw materials (Reaction Formula 17)
[0157]
[0158] Under argon atmosphere, olefin substrate 1a (0.1mmol, 16.2mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and N-methyl-N-benzylaniline 2h (0.25mmol, 47μL) and benzoyl fluoride (0.4mmol, 44μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W 460nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=20:1-10:1) to obtain the target product 4bg.
[0159] The product testing data are as follows:
[0160] Yellow oil, yield 52%.
[0161] 1 H NMR (400MHz, CDCl3): δ7.94(d,J=8.4Hz,2H),7.85(d,J=7.2Hz,2H),7.45(t,J=7.6Hz,1H),7.37–7.14(m,12H),6.68(t,J=4 .0Hz,3H),4.62(dd,J=8.0,6.0Hz,1H),4.48(s,2H),3.87(s,3H),3.48–3.30(m,2H),2.66–2.57(m,1H),2.15–2.09(m,1H).
[0162] 13 C NMR (100MHz, CDCl3): δ198.6,166.7,148.4,144.4,138.9,136.3,133.2,130.4,129.3,129 .2,128.7,128.6,128.6,128.2,126.9,126.7,116.7,112.7,54.9,52.1,51.2,49.3,31.4.
[0163] Example 18 Using 4-vinylbenzoic acid methyl ester, N,N-dimethylaniline and 4-methylbenzoyl fluoride as raw materials (reaction formula 18)
[0164]
[0165]
[0166]
[0167] Under argon atmosphere, olefin substrate 1a (0.1mmol, 16.2mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and N,N-dimethylaniline (0.25mmol, 32μL) and 4-tert-butylbenzoyl fluoride 3c (0.4mmol, 66μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W 460nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=20:1-10:1) to obtain the target product 4cb.
[0168] The product testing data are as follows:
[0169] Yellow oil, yield 64%.
[0170] 1 H NMR (400MHz, CDCl3): δ7.97 (d, J = 8.0 Hz, 2H), 7.86 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.0 Hz, 4H), 7.19 (t, J = 7.6 Hz, 2H), 6.67 (t, J = 10. 0Hz,3H),4.66(t,J=7.2Hz,1H),3.88(s,3H),3.40–3.23(m,2H),2.88(s,3H),2.60–2.51(m,1H),2.11–2.02(m,1H),1.30(s,9H).
[0171] 13 C NMR (100MHz, CDCl3): δ198.2,166.8,157.0,149.3,144.8,133.8,130.3,129.2,12 9.1,128.7,128.3,125.6,116.5,112.6,52.1,50.9,50.8,38.3,35.1,31.1,31.0.
[0172] Example 20 Using 4-vinylbenzoic acid methyl ester, N,N-dimethylaniline and 4-chlorobenzoyl fluoride as raw materials (reaction formula 20)
[0173]
[0174] Under argon environment, olefin substrate 1a (0.1mmol, 16.2mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and N,N-dimethylaniline (0.25mmol, 32μL) and 4-chlorobenzoyl fluoride 3d (0.4mmol, 49μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W460nmLED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=20:1-10:1) to obtain the target product 4cc.
[0175] The product testing data are as follows:
[0176] Yellow oil, yield 72%.
[0177] 1 H NMR (400MHz, CDCl3): δ7.98(d,J=8.4Hz,2H),7.80(d,J=8.8Hz,2H),7.34(t,J=8.4Hz,4H),7.18(dd,J=8.8,7.2Hz,2H),6.71– 6.64(m,3H),4.59(dd,J=8.4,6.0Hz,1H),3.89(s,3H),3.39–3.26(m,2H),2.86(s,3H),2.60–2.51(m,1H),2.11–2.03(m,1H).
[0178] 13 C NMR (100MHz, CDCl3): δ197.5,166.7,149.3,144.2,139.6,134.6,130.4,130 .0,129.3,129.2,129.0,128.2,116.7,112.6,52.2,51.0,50.6,38.4,31.1.
[0179] Implementation Case 21
[0180] Using 4-vinylbenzoic acid methyl ester, N,N-dimethylaniline and 4-methoxybenzoyl fluoride as raw materials (reaction formula 21)
[0181]
[0182] Under argon atmosphere, olefin substrate 1a (0.1mmol, 16.2mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and then N,N-dimethylaniline (0.25mmol, 32μL) and 4-methoxybenzoyl fluoride 3e (0.4mmol, 48μL) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W460nmLED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=10:1-5:1) to obtain the target product 4cd.
[0183] The product testing data are as follows:
[0184] Yellow oil, yield 58%.
[0185] 1 H NMR (400MHz, CDCl3): δ7.96(d,J=8.4Hz,2H),7.89(d,J=8.8Hz,2H),7.37(d,J=8.4Hz,2H),7.19(dd,J=8.8,7.2Hz,2H),6.84(d,J=8.8Hz,2H),6 .70–6.65(m,3H),4.61(dd,J=8.0,6.0Hz,1H),3.88(s,3H),3.82(s,3H) ,3.39–3.24(m,2H),2.87(s,3H),2.58–2.49(m,1H),2.10–2.01(m,1H).
[0186] 13 C NMR (100MHz, CDCl3): δ197.2,166.8,163.6,149.3,145.0,131.0,130.3,129.4 ,129.2,129.0,128.2,116.5,113.8,112.5,55.5,52.1,50.7,50.6,38.4,31.1.
[0187] Example 22 Using 4-vinylbenzoic acid methyl ester, N,N-dimethylaniline and 4-phenylbenzoyl fluoride as raw materials (reaction formula 22)
[0188]
[0189] Under argon atmosphere, olefin substrate 1a (0.1mmol, 16.2mg), photocatalyst (0.002mmol, 1.9mg), nitrogen heterocyclic carbene (0.02mmol, 4.9mg), cesium carbonate (0.1mmol, 32.5mg), potassium bicarbonate (0.05mmol, 5mg) were added to a dry 10mL reaction tube, 2mL acetonitrile was added, and then N,N-dimethylaniline (0.25mmol, 32μL) and 4-phenylbenzoyl fluoride 3f (0.4mmol, 80mg) were added to the reaction tube. The reaction was placed at room temperature and stirred under 12W 460nm LED blue light until the raw materials disappeared. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, the solvent was dried under vacuum decompression, and filtered with a silica gel column (PE:EA=10:1-5:1) to obtain the target product 4ce.
[0190] The product testing data are as follows:
[0191] White solid, yield 46%.
[0192] 1 H NMR (400MHz, CDCl3): δ7.98(dd,J=8.4,6.8Hz,4H),7.58(t,J=8.4Hz,4H),7.47–7.38(m,5H),7.19(dd,J=8.8,7.2Hz,2H),6.68( t,J=7.2Hz,3H),4.69(dd,J=8.4,6.4Hz,1H),3.89(s,3H),3.42–3.28(m,2H),2.89(s,3H),2.63–2.54(m,1H),2.14–2.05(m,1H).
[0193] 13 C NMR (100MHz, CDCl3): δ198.2,166.8,149.3,145.9,144.6,139.7,135.0,130.4,129.3,1 29.23,129.18,129.0,128.3,127.3,127.2,116.6,112.6,52.1,51.0,50.7,38.4,31.2.
Claims
1. A method for synthesizing γ-aminoketone, characterized in that styrene, N,N-dimethylaniline and benzoyl fluoride are used as substrates, (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate is used as a photocatalyst, 3-ethylbenzo[d]thiazol-3-ium bromide is used as a nitrogen heterocyclic carbene, cesium carbonate and potassium bicarbonate are used as a base, acetonitrile is used as a solvent, and the γ-aminoketone is obtained by reacting at room temperature for 4 hours under visible light 12W 460nm LED blue light, and the reaction is as follows: Where R 1 is selected from ester, chloro, naphthalene, phenyl, cyano, pyridine; R 2 Selected from phenyl, thiophene; R 3 is selected from methyl, chloro, ester, cyano; R 4 is selected from ethyl, phenyl, benzyl; R 5 Selected from methyl, tert-butyl, phenyl, chloro, methoxy.
2. The method for synthesizing γ-aminoketone according to claim 1, characterized in that: The photocatalyst is selected from (4,4'-di-tert-butyl-2,2'-bipyridyl)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate.
3. The method for synthesizing γ-aminoketone according to claim 1, characterized in that: The nitrogen heterocyclic carbene is selected from 3-ethylbenzo[d]thiazol-3-ium bromide.
4. The method for synthesizing γ-aminoketone according to claim 1, characterized in that: The base is selected from cesium carbonate and potassium bicarbonate.
5. The method for synthesizing γ-aminoketone according to claim 1, characterized in that: The solvent is selected from acetonitrile.
6. The method for synthesizing γ-aminoketone according to claim 1, characterized in that: Visible light is selected from 12W460nm LED blue light.
7. The method for synthesizing γ-aminoketone according to claim 1, characterized in that: The reaction temperature is selected from 25-30°C and maintained for 4 hours.