CN112441935B - Synthesis method of beta-aminoketone compound - Google Patents
Synthesis method of beta-aminoketone compound Download PDFInfo
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- CN112441935B CN112441935B CN201910794197.3A CN201910794197A CN112441935B CN 112441935 B CN112441935 B CN 112441935B CN 201910794197 A CN201910794197 A CN 201910794197A CN 112441935 B CN112441935 B CN 112441935B
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- 238000001308 synthesis method Methods 0.000 title description 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 50
- 239000002904 solvent Substances 0.000 claims abstract description 42
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 26
- JLTDJTHDQAWBAV-UHFFFAOYSA-N phenyldimethylamine Natural products CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 17
- 239000000126 substance Substances 0.000 claims abstract description 13
- 239000000758 substrate Substances 0.000 claims abstract description 13
- -1 N, N-dimethylaniline compound Chemical class 0.000 claims abstract description 8
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 7
- 238000005286 illumination Methods 0.000 claims abstract description 3
- 239000011261 inert gas Substances 0.000 claims abstract description 3
- 238000002156 mixing Methods 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 35
- 238000004440 column chromatography Methods 0.000 claims description 34
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- 239000003480 eluent Substances 0.000 claims description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 17
- 239000003208 petroleum Substances 0.000 claims description 17
- 239000000741 silica gel Substances 0.000 claims description 17
- 229910002027 silica gel Inorganic materials 0.000 claims description 17
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
- 238000010626 work up procedure Methods 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 abstract description 4
- 238000007146 photocatalysis Methods 0.000 abstract description 3
- 230000001699 photocatalysis Effects 0.000 abstract description 3
- 238000005265 energy consumption Methods 0.000 abstract description 2
- 238000007306 functionalization reaction Methods 0.000 abstract description 2
- 239000002912 waste gas Substances 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 60
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- 238000012512 characterization method Methods 0.000 description 15
- 238000004821 distillation Methods 0.000 description 15
- 239000007788 liquid Substances 0.000 description 15
- 239000000463 material Substances 0.000 description 15
- 239000012299 nitrogen atmosphere Substances 0.000 description 12
- 239000012295 chemical reaction liquid Substances 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 150000004699 copper complex Chemical class 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
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 hours under the conditions of illumination of a blue LED, temperature of 15-40 ℃ and protection of inert gas, 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 produce 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-amino ketones (shown below). The beta-aminoketone is also an important bioactive substance, and has various biological activities of relieving cough, resisting bacteria, resisting inflammation and cancer, resisting virus, tranquilizing, relieving pain, lowering 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 aromatic amine 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 of the solvent is 10-20 mL/mmol based on the substance 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 a reaction solution, evaporating under reduced pressure to remove a solvent, and performing column chromatography separation, wherein the volume ratio of petroleum ether to ethyl acetate is 10:1 as eluent, collecting eluent containing a target product, evaporating the solvent and drying to obtain a beta-aminoketone compound (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) of the present invention is 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 invention
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. Then, under the irradiation of 15w Blue LED, reacting for 8h under the condition of 25 ℃ and nitrogen atmosphere, after the reaction is finished, adding two-spoon column chromatography silica gel (100-200 meshes), removing the solvent by reduced pressure distillation, and separating by column chromatography to obtain the pure product (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-fluorobenzonitrile (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 addition of 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-benzsuccinimide (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, 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 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-Enyloxy-4-pentyloxybenzosuccinimide (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 solvent. Then, under the irradiation of 15w Blue LED, reacting for 8h under the condition of 25 ℃ and nitrogen atmosphere, after the reaction is finished, adding two-spoon column chromatography silica gel (100-200 meshes), removing the solvent by reduced pressure distillation, and separating by column chromatography to obtain the pure product (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-Enyloxy-3-fluorobenzocytidimide (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 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 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 data: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. Then, under the irradiation of 15w Blue LED, reacting for 8h under the condition of 25 ℃ and nitrogen atmosphere, after the reaction is finished, adding two-spoon column chromatography silica gel (100-200 meshes), removing the solvent by reduced pressure distillation, and separating by column chromatography to obtain the pure product (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 a 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 a 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 a solvent. Then, under the irradiation of 15w Blue LED, reacting for 5h under the condition of 25 ℃ and nitrogen atmosphere, after the reaction is finished, adding two-spoon column chromatography silica gel (100-200 meshes), removing the solvent by reduced pressure distillation, and separating by column chromatography to obtain the pure product (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. Then, under the irradiation of 15w Blue LED, reacting for 10h under the condition of 25 ℃ and nitrogen atmosphere, after the reaction is finished, adding two-spoon column chromatography silica gel (100-200 meshes), removing the solvent by reduced pressure distillation, and separating by column chromatography to obtain the pure product (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 a β -aminoketone compound (III), 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 hours under the conditions of illumination of a blue LED, temperature of 15-40 ℃ and protection of inert gas, 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 compounds shown in 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 compound (III) 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 compound (III) according to claim 1, wherein the volume usage of the solvent is 10 to 20mL/mmol based on the substance amount of the substrate (I).
4. The process for the synthesis of β -aminoketones (III) according to claim 1, characterized in that the work-up is carried out by: and after the reaction is finished, adding column chromatography silica gel into the reaction solution, distilling under reduced pressure to remove the solvent, and performing column chromatography separation by using petroleum ether and ethyl acetate in a volume ratio of 10:1 as eluent, collecting eluent containing target product, evaporating solvent and drying to obtain beta-aminoketone compound (III).
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