CN112441935A - Synthesis method of beta-aminoketone compound - Google Patents
Synthesis method of beta-aminoketone compound Download PDFInfo
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Abstract
A method of synthesizing a β -aminoketone compound, the method comprising: mixing a substrate (I), a photosensitizer, an N, N-dimethylaniline compound (II), an alkaline substance and a solvent, reacting for 5-10 h under the conditions of blue LED illumination, temperature of 15-40 ℃ and inert gas protection, and then carrying out post-treatment on a reaction solution to obtain a beta-aminoketone compound (III); the invention is safe and environment-friendly, does not generate waste gas and has low operation risk; the substrate has good adaptability, and various substituents can realize dual-functionalization; the reaction condition is mild; meanwhile, the reaction has certain innovativeness, the traditional heating mode is replaced by a photocatalysis mode, the energy consumption is reduced, and the method is more in line with the modern green chemistry concept;
Description
(I) technical field
The invention relates to a method for synthesizing beta-aminoketone compounds.
(II) background of the invention
Beta-aminoketones are key intermediates for the synthesis of pharmaceuticals and natural products (beta-aminoalcohols, beta-amino acids, beta-lactams) and have a wide range of uses in organic synthesis. Various types of compounds can be synthesized via beta-aminoketones (as shown below). The beta-aminoketone is also an important bioactive substance and has a plurality of biological activities of relieving cough, resisting bacteria, resisting inflammation and cancer, resisting viruses, tranquilizing, relieving pain, reducing blood pressure, inhibiting edema, resisting blood coagulation and the like. Due to the wide application of the compounds in the medicine and chemical industry, great attention is paid to synthetic chemists.
The beta-aminoketone compound is synthesized in the early stage by taking acetophenone, aromatic aldehyde and arylamine as raw materials and adopting a one-pot Mannich reaction to synthesize the beta-aminoketone compound and derivatives thereof. In recent years, with intensive research on a synthesis method of a β -aminoketone compound, researchers have developed a series of new synthesis methods, for example, 2009 (org. lett.2009,11, 3730-containing 3733) et al report that a trimethylsilyl alkenyl ether compound is used as a substrate, an N, N-dimethylaniline compound is used as a nitrogen source, di-tert-butyl peroxide is used as an oxidant, cuprous bromide is used as a catalyst, acetonitrile is used as a solvent, and the reaction is carried out at 60 ℃ for 12 hours to obtain a target product β -aminoketone, which needs to be carried out under a heating condition while adding an oxidant, namely di-tert-butyl peroxide, wherein the oxidant has a large uncontrollable factor under the heating condition and is easy to explode. Based on the synthetic disadvantages of such methods, we felt that it is very necessary to find a green, mild reaction condition. The invention adopts a photocatalysis method closer to the green chemical concept, and under the condition of room temperature, N-alkenyloxy-benzosuccinimide and N, N-dimethylaniline are used as raw materials, a cheap metal copper complex is used as a photosensitizer, and a series of functionalized beta-aminoketone compounds are generated under the catalysis of 15W blue light. The reaction conditions are mild, the operation is simple, and cheap copper is used as a photosensitizer. Through the development of reaction substrates, the reaction shows better substrate universality.
Disclosure of the invention
Aiming at the defects of the prior art, the invention provides a universal, simple and efficient method for synthesizing beta-aminoketone compounds.
The technical scheme of the invention is as follows:
a method of synthesizing a β -aminoketone compound, the method comprising:
mixing a substrate (I), a photosensitizer, an N, N-dimethylaniline compound (II), an alkaline substance and a solvent, reacting for 5-10 h (preferably 8h) under the conditions of illumination of a blue LED (15w), temperature of 15-40 ℃ (preferably 25 ℃), and inert gas protection, and then carrying out post-treatment on a reaction solution to obtain a beta-aminoketone compound (III);
the ratio of the substrate (I), the photosensitizer, the N, N-dimethylaniline compound (II) and the alkaline substance is 1: 0.01-0.05: 1-3: 1-3, preferably 1: 0.02: 2: 2;
the volume usage amount of the solvent is 10-20 mL/mmol based on the substance amount of the substrate (I);
the photosensitizer is one or a mixture of two of the compounds shown in the formulas (IV) and (V) in any proportion;
the alkaline substance is one or a mixture of two of potassium carbonate and cesium carbonate in any proportion;
the solvent is one or a mixed solvent of more than two of acetonitrile, tetrahydrofuran and 1, 4-dioxane in any proportion, preferably acetonitrile;
the post-treatment method comprises the following steps: after the reaction is finished, adding column chromatography silica gel (100-200 meshes) into the reaction solution, evaporating under reduced pressure to remove the solvent, and performing column chromatography separation, wherein the volume ratio of petroleum ether to ethyl acetate is 10:1 as eluent, collecting eluent containing target products, evaporating the solvent and drying to obtain beta-aminoketone compounds (III);
the reaction formula is as follows:
in formula (I), formula (II) or formula (III),
R1is hydrogen, methyl, fluorine, chlorine, bromine or pentyloxy;
R2is hydrogen or bromine;
the structural formula of the photosensitizer is as follows:
specifically, the β -aminoketones (III) according to the present invention are preferably one of the following compounds:
compared with the prior art, the invention has the beneficial effects that:
(1) the method is safe and environment-friendly, does not generate waste gas, and has low operation risk;
(2) the substrate has good adaptability, and various substituents can realize dual-functionalization;
(3) the reaction condition is mild;
(4) meanwhile, the reaction has certain innovativeness, the traditional heating mode is replaced by a photocatalysis mode, the energy consumption is reduced, and the method is more in line with the modern green chemistry concept.
(IV) detailed description of the preferred embodiments
The invention will be further illustrated by the following examples, without limiting the scope of the invention:
example 1
2-N-alkenyloxybenzsuccinimide (0.3mmol, 0.0792g), photosensitizer (IV) (0.006mmol, 0.0067g), N-dimethylaniline (0.6mmol, 0.0726g) and potassium carbonate (0.6mmol, 0.0828g) were added to a 15mL Schlenk reaction tube, followed by 3mL acetonitrile as solvent. Then, under the irradiation of 15w Blue LED, the reaction is carried out for 8h under the condition of 25 ℃ and the nitrogen environment, after the reaction is finished, two spoons (0.5g) of column chromatography silica gel (100 meshes and 200 meshes) are added into the reaction liquid, the solvent is removed by reduced pressure distillation, and then the product pure product shown in the structural formula is obtained by column chromatography separation (petroleum ether/ethyl acetate-10: 1 is used as eluent). The material was a yellow liquid in 65% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ7.93～7.91(m,2H),7.57～7.53(m,1H),7.46～7.42(m, 2H),7.26～7.23(m,2H),6.75～6.70(m,3H),3.83(t,J＝7.0Hz,2H),3.23(t,J＝7.0Hz,2H),2.96(s, 3H).13C NMR(125MHz,CDCl3)δ199.49,148.56,136.84,133.22,129.32,128.62,128.02,116.53, 112.34,47.92,38.51,35.13.
example 2
2-N-Enyloxy-4-methylbenzenesuccinimide (0.3mmol, 0.0834g), photosensitizer (V) (0.006mmol, 0.007 g), N-dimethylaniline (0.6mmol, 0.0726g) and potassium carbonate (0.6mmol, 0.0828g) were added to a 15mL Schlenk reaction tube, followed by 3mL of acetonitrile as solvent. And then, reacting for 8 hours under the condition of 25 ℃ and nitrogen atmosphere under the irradiation of 15w Blue LED, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating by column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 60% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ7.85(d,J＝8.2Hz,2H),7.29～7.26(m,4H),6.78～6.73 (m,3H),3.85(t,J＝7.0Hz,2H),3.23(t,J＝7.0Hz,2H),2.99(s,3H),2.43(s,3H).13C NMR(125 MHz,CDCl3)δ199.14,148.64,144.04,134.47,129.32,129.31,128.17,116.52,112.38,48.07,38.50, 35.05,21.62.
example 3
2-N-alkenyloxy-4-fluorobenzocylindimide (0.3mmol, 0.0846g), photosensitizer (IV) (0.003mmol, 0.0033g), N-dimethylaniline (0.6mmol, 0.0726g) and potassium carbonate (0.6mmol, 0.0828g) were added to a 15mL Schlenk reaction tube, followed by 3mL of acetonitrile as a solvent. And then, reacting for 8 hours under the condition of 25 ℃ and nitrogen atmosphere under the irradiation of 15w Blue LED, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating by column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 57% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ8.00～7.96(m,2H),7.30～7.27(m,2H),7.17～7.13(m, 2H),6.78～6.75(m,3H),3.87(t,J＝7.0Hz,2H),3.24(t,J＝7.0Hz,2H)),3.00(s,3H).13C NMR(125 MHz,CDCl3)δ197.91,165.82(d,J＝253.5Hz),164.81,148.54,133.34(d,J＝3.0Hz),130.69(d,J＝9.3 Hz),129.37,116.65,115.82,115.65,112.40,47.96,38.58,35.11.
example 4
2-N-Enyloxy-4-chloro-benzosuccinimide (0.3mmol, 0.0894g), photosensitizer (IV) (0.015mmol, 0.0167 g), N-dimethylaniline (0.6mmol, 0.0726g) and potassium carbonate (0.6mmol, 0.0828g) were added to a 15mL Schlenk reaction tube, and 3mL of acetonitrile was added as a solvent. And then, reacting for 8 hours under the condition of 25 ℃ and nitrogen atmosphere under the irradiation of 15w Blue LED, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating by column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 64% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ7.86(d,J＝8.6Hz,2H),7.42(d,J＝8.6Hz,2H),7.26(dd, J1＝9.0,J2＝7.1Hz,2H),6.74(d,J＝7.8,6.4Hz,3H),3.84(t,J＝7.0Hz,2H),3.21(t,J＝7.0Hz,2H), 2.97(s,3H).13C NMR(125MHz,CDCl3)δ198.29,148.50,139.69,135.17,129.5,129.4,128.94,116.69, 112.40,47.91,38.59,35.17.
example 5
2-N-Enyloxy-4-bromo-benzosuccinimide (0.3mmol, 0.1026g), photosensitizer (IV) (0.006mmol, 0.0067g), N-dimethylaniline (0.3mmol, 0.0363g) and potassium carbonate (0.6mmol, 0.0828g) were added to a 15mL Schlenk reaction tube, followed by 3mL acetonitrile as a solvent. And then, reacting for 8 hours under the condition of 25 ℃ and nitrogen atmosphere under the irradiation of 15w Blue LED, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating by column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 51% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ7.83～7.80(m,2H),7.63～7.60(m,2H),7.30–7.28(m, 2H),6.78～6.76(m,3H),3.86(t,J＝7.0Hz,2H),3.23(t,J＝7.0Hz,2H)),3.00(s,3H).13C NMR(125 MHz,CDCl3)δ198.52,148.49,135.56,131.96,129.57,129.38,128.65,116.69,112.39,47.89,38.61, 35.15.
example 6
2-N-alkenyloxy-4-pentyloxybenzsuccinimide (0.3mmol, 0.1050g), photosensitizer (IV) (0.006mmol, 0.0067g), N-dimethylaniline (0.9mmol, 0.1089g) and potassium carbonate (0.6mmol, 0.0828g) were added to a 15mL Schlenk reaction tube, and 3mL of acetonitrile was added as a solvent. And then, reacting for 8 hours under the condition of 25 ℃ and nitrogen atmosphere under the irradiation of 15w Blue LED, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating by column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 63% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ7.93(d,J＝8.9Hz,2H),7.30～7.27(m,2H),6.94(t,J＝ 5.5Hz,2H),6.79～6.75(m,3H),4.04(t,J＝6.5Hz,2H),3.87～3.83(m,2H),3.23～3.19(m,2H), 3.00(s,3H),1.85～1.82(m,2H),1.49～1.42(m,4H),0.99–0.96(m,3H).13C NMR(125MHz,CDCl3) δ198.03,163.25,148.64,130.33,129.81,129.32,116.47,114.21,112.36,68.27,48.19,38.50,34.76, 28.78,28.11,22.41,13.98.
example 7
2-N-Enyloxy-2-methylbenzenesuccinimide (0.3mmol, 0.0834g), photosensitizer (IV) (0.006mmol, 0.0067g), N-dimethylaniline (0.6mmol, 0.0726g) and potassium carbonate (0.3mmol, 0.0414g) were added to a 15mL Schlenk reaction tube, followed by 3mL of acetonitrile as a solvent. And then, reacting for 8 hours under the condition of 25 ℃ and nitrogen atmosphere under the irradiation of 15w Blue LED, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating by column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 51% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ7.77(dd,J1＝7.7,J2＝0.9Hz,2H),7.35(td,J＝7.5,1.2 Hz,2H),7.28～7.21(m,4H),3.31(s,4H),2.48(s,6H).13C NMR(125MHz,CDCl3)δ202.65,138.03, 137.87,131.86,131.25,128.53,125.67,35.63,21.19.
example 8
2-N-alkenyloxy-3-fluorobenzocylindimide (0.3mmol, 0.0846g), photosensitizer (IV) (0.006mmol, 0.0067g), N-dimethylaniline (0.6mmol, 0.0726g) and potassium carbonate (0.9mmol, 0.1242g) were added to a 15mL Schlenk reaction tube, followed by 3mL acetonitrile as solvent. And then, reacting for 8 hours under the condition of 25 ℃ and nitrogen atmosphere under the irradiation of 15w Blue LED, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating by column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 65% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ7.68(d,J＝7.8Hz,1H),7.61～7.58(m,1H),7.43～7.38 (m,1H),7.26～7.22(m,3H),6.73(d,J＝7.5Hz,3H),3.82(t,J＝7.0Hz,2H),3.19(t,J＝7.0Hz,2H)), 2.96(s,3H).13C NMR(125MHz,CDCl3)δ198.20,162.84(d,J＝246.63Hz),161.86,148.47,138.90(d, J＝6.0Hz),130.30(d,J＝7.6Hz),129.35,123.80(d,J＝3.0Hz),120.32,120.14,116.67,114.80,114.62, 112.38,47.79,38.55,35.34.
example 9
2-N-alkenyloxy-3-methylbenzenesuccinimide (0.3mmol, 0.0834g), photosensitizer (IV) (0.006mmol, 0.0067g), N-dimethylaniline (0.6mmol, 0.0726g) and potassium carbonate (0.6mmol, 0.0828g) were added to a 15mL Schlenk reaction tube, and 3mL of tetrahydrofuran was added as a solvent. And then, reacting for 8 hours under the condition of 25 ℃ and nitrogen atmosphere under the irradiation of 15w Blue LED, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating by column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 53% yield.
Characterization ofData:1H NMR(500MHz,CDCl3)δ7.67～7.62(m,2H),7.26～7.23(m,2H),7.19～7.15(m, 2H),6.67～6.63(m,3H),3.74(t,J＝7.0Hz,2H),3.14(t,J＝7.0Hz,2H),2.89(s,3H),2.31(s,3H). 13C NMR(125MHz,CDCl3)δ199.75,148.57,138.43,136.90,133.98,129.33,128.6,128.5,125.24, 116.50,112.35,47.97,38.53,35.18,21.31.
example 10
2-N-alkenyloxy-4-bromobenzosuccinimide (0.3mmol, 0.1026g), photosensitizer (IV) (0.006mmol, 0.0067g), N-dimethylaniline (0.6mmol, 0.0726g) and potassium carbonate (0.6mmol, 0.0828g) were added to a 15mL Schlenk reaction tube, followed by 3mL of 1, 4-dioxane as solvent. And then, reacting for 8 hours under the condition of 25 ℃ and nitrogen atmosphere under the irradiation of 15w Blue LED, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating by column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 60% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ8.04(t,J＝1.8Hz,1H),7.83～7.81(m,1H),7.68～7.65 (m,1H),7.31(t,J＝7.9Hz,1H),7.26～7.23(m,2H),6.74～6.71(m,3H),3.82(t,J＝7.0Hz,2H), 3.19(t,J＝7.0Hz,2H),2.96(s,3H).13C NMR(125MHz,CDCl3)δ198.08,148.44,138.52,136.04, 131.10,130.21,129.36,126.53,123.00,116.70,112.39,47.77,38.58,35.28.
example 11
2-N-alkenyloxybenzsuccinimide (0.3mmol, 0.1026g), photosensitizer (IV) (0.006mmol, 0.0067g), N-dimethyl-3-bromoaniline (0.6mmol, 0.1194g) and potassium carbonate (0.6mmol, 0.0828g) were added to a 15mL Schlenk reaction tube, followed by 3mL acetonitrile as solvent. And then, reacting for 8 hours under the condition of 15w of Blue LED irradiation and 15 ℃ in a nitrogen environment, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating through column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 62% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ7.86～7.83(m,2H),7.51～7.47(m,1H),7.38(dd,J1＝ 11.0,J2＝4.5Hz,2H),6.99(t,J＝8.1Hz,1H),6.75～6.72(m,2H),6.57～6.54(m,1H),3.72(t,J＝8.0 Hz,2H),3.14(t,J＝7.0Hz,2H),2.87(s,3H).13C NMR(125MHz,CDCl3)δ199.14,147.52,136.70, 133.30,131.90,128.64,127.97,113.89,108.39,47.89,38.58,34.96.
example 12
2-N-alkenyloxybenzsuccinimide (0.3mmol, 0.1026g), photosensitizer (IV) (0.006mmol, 0.0067g), N-dimethyl 3-bromoaniline (0.6mmol, 0.1194g) and potassium carbonate (0.6mmol, 0.0828g) were added to a 15mL Schlenk reaction tube, followed by 3mL acetonitrile as solvent. And then, reacting for 8 hours under the condition of 40 ℃ and nitrogen atmosphere under the irradiation of 15w Blue LED, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating by column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 58% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ7.86～7.83(m,2H),7.51～7.47(m,1H),7.38(dd,J1＝ 11.0,J2＝4.5Hz,2H),6.99(t,J＝8.1Hz,1H),6.75～6.72(m,2H),6.57～6.54(m,1H),3.72(t,J＝8.0 Hz,2H),3.14(t,J＝7.0Hz,2H),2.87(s,3H).13C NMR(125MHz,CDCl3)δ199.14,147.52,136.70, 133.30,131.90,128.64,127.97,113.89,108.39,47.89,38.58,34.96.
example 13
2-N-alkenyloxybenzsuccinimide (0.3mmol, 0.1026g), photosensitizer (IV) (0.006mmol, 0.0067g), N-dimethyl-4-bromoaniline (0.6mmol, 0.1194g) and potassium carbonate (0.6mmol, 0.0828g) were added to a 15mL Schlenk reaction tube, followed by 3mL acetonitrile as solvent. And then, reacting for 5 hours under the condition of 25 ℃ and nitrogen atmosphere under the irradiation of 15w Blue LED, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating by column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 49% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ7.92～7.89(m,2H),7.57～7.54(m,1H),7.44(t,J＝7.8 Hz,2H),7.31～7.27(m,2H),6.60～6.56(m,2H),3.79(t,J＝7.0Hz,2H),3.20(t,J＝7.0Hz,2H),2.93 (s,3H).13C NMR(125MHz,CDCl3)δ199.14,147.52,136.70,133.30,131.90,128.64,127.97,113.89, 108.39,47.89,38.58,34.96.
example 14
2-N-alkenyloxybenzsuccinimide (0.3mmol, 0.1026g), photosensitizer (IV) (0.006mmol, 0.0067g), N-dimethyl-4-bromoaniline (0.6mmol, 0.1194g) and potassium carbonate (0.6mmol, 0.0828g) were added to a 15mL Schlenk reaction tube, followed by 3mL acetonitrile as solvent. And then, reacting for 10 hours under the condition of 25 ℃ and nitrogen atmosphere under the irradiation of 15w Blue LED, adding two-spoon column chromatography silica gel (100-200 meshes) into the reaction liquid after the reaction is finished, removing the solvent through reduced pressure distillation, and separating by column chromatography to obtain a pure product (taking petroleum ether/ethyl acetate-10: 1 as an eluent) shown in the structural formula. The material was a yellow liquid in 65% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ7.92～7.89(m,2H),7.57～7.54(m,1H),7.44(t,J＝7.8 Hz,2H),7.31～7.27(m,2H),6.60～6.56(m,2H),3.79(t,J＝7.0Hz,2H),3.20(t,J＝7.0Hz,2H),2.93 (s,3H).13C NMR(125MHz,CDCl3)δ199.14,147.52,136.70,133.30,131.90,128.64,127.97,113.89, 108.39,47.89,38.58,34.96.
example 15
2-N-alkenyloxybenzsuccinimide (0.3mmol, 0.0792g), photosensitizer (IV) (0.006mmol, 0.0067g), N-dimethylaniline (0.6mmol, 0.0726g) and cesium carbonate (0.6mmol, 0.1956g) were added to a 15mL Schlenk reaction tube, followed by 3mL acetonitrile as solvent. Then, under the irradiation of 15w Blue LED, the reaction is carried out for 8h under the condition of 25 ℃ and the nitrogen environment, after the reaction is finished, two spoons (0.5g) of column chromatography silica gel (100 meshes and 200 meshes) are added into the reaction liquid, the solvent is removed by reduced pressure distillation, and then the product pure product shown in the structural formula is obtained by column chromatography separation (petroleum ether/ethyl acetate-10: 1 is used as eluent). The material was a yellow liquid in 57% yield.
Characterization data:1H NMR(500MHz,CDCl3)δ7.93～7.91(m,2H),7.57～7.53(m,1H),7.46～7.42(m, 2H),7.26～7.23(m,2H),6.75～6.70(m,3H),3.83(t,J＝7.0Hz,2H),3.23(t,J＝7.0Hz,2H),2.96(s, 3H).13C NMR(125MHz,CDCl3)δ199.49,148.56,136.84,133.22,129.32,128.62,128.02,116.53, 112.34,47.92,38.51,35.13.
Claims (4)
1. a method for synthesizing beta-aminoketone compounds is characterized by comprising the following steps:
mixing a substrate (I), a photosensitizer, an N, N-dimethylaniline compound (II), an alkaline substance and a solvent, reacting for 5-10 h under the conditions of blue LED illumination, temperature of 15-40 ℃ and inert gas protection, and then carrying out post-treatment on a reaction solution to obtain a beta-aminoketone compound (III);
the ratio of the substrate (I), the photosensitizer, the N, N-dimethylaniline compound (II) and the alkaline substance is 1: 0.01-0.05: 1-3: 1-3;
the photosensitizer is one or a mixture of two of the compounds shown in the formulas (IV) and (V) in any proportion;
the alkaline substance is one or a mixture of two of potassium carbonate and cesium carbonate in any proportion;
the solvent is one or a mixed solvent of more than two of acetonitrile, tetrahydrofuran and 1, 4-dioxane in any proportion;
the reaction formula is as follows:
in formula (I), formula (II) or formula (III),
R1is hydrogen, methyl, fluorine, chlorine, bromine or pentyloxy;
R2is hydrogen or bromine.
2. The method for synthesizing β -aminoketones according to claim 1, wherein the ratio of the amounts of the substrate (I), the photosensitizer, the N, N-dimethylaniline compound (II), and the basic substance is 1: 0.02: 2: 2.
3. the method for synthesizing β -aminoketones according to claim 1, wherein the volume usage of the solvent is 10 to 20mL/mmol based on the amount of the substance of the substrate (I).
4. The method of synthesizing β -aminoketones according to claim 1, wherein the post-treatment method is: after the reaction is finished, adding column chromatography silica gel into the reaction liquid, evaporating the solvent under reduced pressure, and performing column chromatography separation, wherein the volume ratio of petroleum ether to ethyl acetate is 10:1 as eluent, collecting eluent containing target product, evaporating solvent and drying to obtain beta-aminoketone compound (III).
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