Method for preparing quinolinone series compounds by dehydrogenation of dihydroquinolinone series compounds
By using visible light dehydrogenation reactions at room temperature, the use of pyrone ketones and olitoxine peroxide as a catalyst and oxidant, and directly obtains apholine ketone series compounds from dihydrolyroline. The problem of using transition metal and harsh conditions in existing technologies has achieved high -efficiency and low -cost compound preparation.
Patent Information
- Application Number
- CN202411444411.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-16
- Publication Date
- 2025-01-21
AI Technical Summary
In the prior art, metal catalytic oxidation or high temperature and high pressure conditions are often used in the preparation of quinolinone series compounds, and there are defects in the use of transition metals, harsh conditions and high costs.
Visible light-induced free radical dehydrogenation reaction is used, and thioxanthone and tert-butyl benzoyl peroxide are used as catalysts and oxidants to carry out dehydrogenation reaction in anhydrous dichloromethane, which is directly prepared from dihydroquinolinone series compounds. Obtain quinolinone series compounds.
It achieves the efficient preparation of quinolinone series compounds at room temperature in a short time, avoids the use of transition metals, is compatible with a variety of functional groups, is simple to operate, has cheap and easily available catalysts, and has wide applicability.
Smart Images
Figure BDA0005087312660000021 
Figure BDA0005087312660000031 
Figure BDA0005087312660000032
Abstract
Description
Technical Field
[0001] The invention belongs to the field of organic synthesis methodology, and specifically relates to a method for preparing quinolinone series compounds by dehydrogenating dihydroquinolinone series compounds. Background Art
[0002] The nitrogen heterocyclic skeleton is an indispensable structure in many organic and biochemical molecules. Among nitrogen heterocyclic compounds, quinolinone is one of the most typical skeletons. The quinolinone skeleton is widely present in various types of natural products, such as different alkaloids isolated from plants or microorganisms. In recent years, quinolinone series compounds have been shown to have antibacterial, antifungal, and anthelmintic activities, and have been widely used in the fields of medicinal chemistry and agricultural chemistry. (Liu K.; Zhang J.; Zhang G. et al. Deciphering Deoxynybomycin Biosynthesis Reveals Fe(II) / α-Ketoglutarate-Dependent Dioxygenase-Catalyzed Oxazoline Ring Formation and Decomposition. J. Am. Chem. Soc. 2023, 145, 27886-27899.) Therefore, the synthesis of quinolinone series compounds has always been a hot direction, and the dehydrogenation of dihydroquinolinone series compounds is an important method for preparing quinolinone series compounds. Traditionally, the dehydrogenation of dihydroquinolinone compounds mainly adopts metal-catalyzed oxidation or AIBN or DDQ oxidation strategies. Based on the basic principle of free radical dehydrogenation, the present invention proposes a new photocatalytic dehydrogenation method, which does not use transition metals, has mild reaction conditions, and the catalyst is cheap and easy to obtain. The substrate has a wide range of applicability and has important research significance. Summary of the invention
[0003] The primary purpose of the present invention is to provide a method for preparing quinolinone series compounds by dehydrogenation of dihydroquinolinone series compounds. The method prepares quinolinone series compounds from dihydroquinolinone series compounds in one step through a free radical dehydrogenation reaction induced by visible light. The present invention provides a general route for preparing quinolinone series compounds by dehydrogenation of dihydroquinolinone series compounds, which does not require transition metal reagents and harsh conditions, is compatible with various types of functional groups, and improves the practicality of this type of reaction.
[0004] In order to achieve the above-mentioned invention object, the present invention adopts the following technical scheme:
[0005] The invention provides a method for preparing quinolinone series compounds by dehydrogenation of dihydroquinolinone series compounds, comprising: under the joint action of visible light irradiation, catalyst and oxidant, the dihydroquinolinone series compounds undergo dehydrogenation reaction in an organic solvent to generate corresponding quinolinone series compounds.
[0006] The general structural formula of the dihydroquinolinone series compounds involved in this patent is:
[0007]
[0008] Furthermore, in a preferred embodiment of the present invention, R 1 is one of methoxy, tert-butyl, hydrogen, bromine, trifluoromethyl, ester, and cyano, R 2 It is one of phenyl, benzyl and hydrogen.
[0009] Furthermore, in a preferred embodiment of the present invention, the visible light is purple LED light with a wavelength of 415nm, and the lamp barrel power is 50W.
[0010] Furthermore, in a preferred embodiment of the present invention, the catalyst is thioxanthone (TX).
[0011] Furthermore, in a preferred embodiment of the present invention, the oxidant is tert-butyl benzoperoxoate.
[0012] Furthermore, in a preferred embodiment of the present invention, the organic solvent is anhydrous dichloromethane (DCM).
[0013] Furthermore, in a preferred embodiment of the present invention, the reaction should be carried out under an argon atmosphere for 10 hours.
[0014] Preferably, the reaction conditions include: the concentration of the dihydroquinolinone series substrates used is 0.02 M, thioxanthone is 5 mol%, tert-butylbenzoyl peroxide is 2 equivalents, and anhydrous dichloromethane is evaporated and used.
[0015] Wherein, the thioxanthone, tert-butyl benzoyl peroxide and dichloromethane described in the present invention are all commercially available.
[0016] In addition, in the present invention, conventional organic synthesis operations such as extraction and spin drying of solvents, including the final silica gel column chromatography separation to obtain the corresponding quinolinone series compounds, belong to the prior art. The extractants and eluents used therein also have ready-made technical support. Those skilled in the art can select appropriate reagents according to the properties of the final product.
[0017] Compared with the prior art, the present invention has the following beneficial effects:
[0018] Through visible light induction, quinolinone series compounds are prepared from dihydroquinolinone series compounds in one step without the use of transition metal catalysis. The reaction time is short and can be carried out at room temperature. The yield of the target product is high, it is compatible with a variety of functional groups, has universal applicability to various types of substrates, the synthetic operation is simple, the catalyst is cheap and easy to obtain, and it has excellent application prospects. DETAILED DESCRIPTION
[0019] The present invention is described in detail below with reference to the examples. The examples are only preferred embodiments of the present invention and are not intended to limit the present invention.
[0020] Example 1
[0021]
[0022] In a clean, dry, sealed reaction vessel, 1a (0.2mmol, 29.6mg), TX (0.01mmol, 2.1mg), anhydrous dichloromethane (10mL), tert-butyl benzoyl peroxide (0.4mmol, 76μL) were added in sequence under an argon atmosphere and placed in a purple LED lamp bucket (wavelength 415nm, power 50W). After reacting at room temperature for 10h, a TLC plate was used to confirm that the reaction was complete (developing agent was PE / EA=1:1). Subsequently, the solvent was removed by a rotary evaporator, and the resulting crude product was separated by silica gel column chromatography (eluent was PE / EA=5:1) to obtain a white solid product 2a with a yield of 62%. The product was characterized by nuclear magnetic resonance as follows:
[0023] 1 H NMR (400MHz, CDCl3) δ12.35(brs,1H),7.83(d,J=9.6Hz,1H),7.60-7.41(m,3H),7.25-7.19(m,1H),6.73(d,J=9.6Hz,1H).
[0024] Example 2
[0025]
[0026] In a clean, dry, sealed reaction vessel, 1b (0.2mmol, 35.6mg), TX (0.01mmol, 2.1mg), anhydrous dichloromethane (10mL), tert-butyl benzoyl peroxide (0.4mmol, 76μL) were added in sequence under an argon atmosphere and placed in a purple LED lamp bucket (wavelength 415nm, power 50W). After reacting at room temperature for 10h, a TLC plate was used to confirm that the reaction was complete (developing agent was PE / EA = 1:1). Subsequently, the solvent was removed by a rotary evaporator, and the resulting crude product was separated by silica gel column chromatography (eluent was PE / EA = 5:1) to obtain a white solid product 2b with a yield of 64%. The product was characterized by nuclear magnetic resonance as follows:
[0027] 1 H NMR (400MHz, CDCl3) δ12.54(brs,1H),7.77(d,J=9.6Hz,1H),7.39(d,J=8.8Hz,1H),7 .16(dd,J=8.8,2.0Hz,1H),6.99(d,J=2.0Hz,1H),6.73(d,J=9.6Hz,1H),3.86(s,3H).
[0028] Example 3
[0029]
[0030] In a clean, dry, sealed reaction vessel, 1c (0.2mmol, 40.9mg), TX (0.01mmol, 2.1mg), anhydrous dichloromethane (10mL), tert-butyl benzoyl peroxide (0.4mmol, 76μL) were added in sequence under an argon atmosphere and placed in a purple LED lamp bucket (wavelength 415nm, power 50W). After reacting at room temperature for 10h, a TLC plate was used to confirm that the reaction was complete (developing agent was PE / EA = 1:1). Subsequently, the solvent was removed by a rotary evaporator, and the resulting crude product was separated by silica gel column chromatography (eluent was PE / EA = 5:1) to obtain a white solid product 2c with a yield of 67%. The product was characterized by NMR as follows:
[0031] 1 H NMR (400MHz, CDCl3) δ12.31(brs,1H),7.80(d,J=9.6Hz,1H),7.58(dd,J=8.8,1.6Hz, 1H),7.52(d,J=1.6Hz,1H),7.39(d,J=8.8Hz,1H),6.71(d,J=9.6Hz,1H),1.36(s,9H).
[0032] Example 4
[0033]
[0034] In a clean, dry, sealed reaction vessel, 1d (0.2mmol, 32.4mg), TX (0.01mmol, 2.1mg), anhydrous dichloromethane (10mL), tert-butyl benzoyl peroxide (0.4mmol, 76μL) were added in sequence under an argon atmosphere and placed in a purple LED lamp bucket (wavelength 415nm, power 50W). After reacting at room temperature for 10h, a TLC plate was used to confirm that the reaction was complete (developing agent was PE / EA = 1:1). Subsequently, the solvent was removed by a rotary evaporator, and the resulting crude product was separated by silica gel column chromatography (eluent was PE / EA = 5:1) to obtain a white solid product 2d with a yield of 51%. The product was characterized by nuclear magnetic resonance as follows:
[0035] 1 H NMR (400MHz, CDCl3) δ9.56(brs,1H),7.77(d,J=9.6Hz,1H),7.42(d,J=8.0Hz,1H ),7.35(d,J=7.2Hz,1H),7.17-7.09(m,1H),6.67(d,J=9.6Hz,1H),2.50(s,3H).
[0036] Example 5
[0037]
[0038] In a clean, dry, sealed reaction vessel, 1e (0.2mmol, 45.2mg), TX (0.01mmol, 2.1mg), anhydrous dichloromethane (10mL), tert-butyl benzoyl peroxide (0.4mmol, 76μL) were added in sequence under an argon atmosphere and placed in a purple LED lamp bucket (wavelength 415nm, power 50W). After reacting at room temperature for 10h, a TLC plate was used to confirm that the reaction was complete (developing agent was PE / EA=1:1). Subsequently, the solvent was removed by a rotary evaporator, and the resulting crude product was separated by silica gel column chromatography (eluent was PE / EA=5:1) to obtain a white solid product 2e with a yield of 52%. The product was characterized by NMR as follows:
[0039] 1 H NMR (400MHz, DMSO-d6) δ11.85(brs,1H),7.93-7.83(m,2H),7.63(dd,J=8.8,2.4Hz,1H),7.24(d,J=8.8Hz,1H),6.55(d,J=9.6Hz,1H).
[0040] Example 6
[0041]
[0042] In a clean, dry, sealed reaction vessel, 1f (0.2mmol, 41.4mg), TX (0.01mmol, 2.1mg), anhydrous dichloromethane (10mL), tert-butyl benzoyl peroxide (0.4mmol, 76μL) were added in sequence under an argon atmosphere and placed in a purple LED lamp bucket (wavelength 415nm, power 50W). After reacting at room temperature for 10h, a TLC plate was used to confirm that the reaction was complete (developing agent was PE / EA = 1:1). Subsequently, the solvent was removed by a rotary evaporator, and the resulting crude product was separated by silica gel column chromatography (eluent was PE / EA = 5:1) to obtain a white solid product 2f with a yield of 47%. The product was characterized by NMR as follows:
[0043] 1 H NMR (400MHz, DMSO-d6) δ12.05(brs,1H),8.33(d,J=1.6Hz,1H),8.08-8.00(m,2H),7.37(d,J=8.4Hz,1H),6.57(d,J=9.6Hz,1H),3.86(s,3H).
[0044] Example 7
[0045]
[0046] In a clean, dry, sealed reaction vessel, 1g (0.2mmol, 47.8mg), TX (0.01mmol, 2.1mg), anhydrous dichloromethane (10mL), tert-butyl benzoyl peroxide (0.4mmol, 76μL) were added in sequence under an argon atmosphere and placed in a purple LED lamp bucket (wavelength 415nm, power 50W). After reacting at room temperature for 10h, a TLC plate was used to confirm that the reaction was complete (developing agent was PE / EA = 1:1). Subsequently, the solvent was removed by a rotary evaporator, and the resulting crude product was separated by silica gel column chromatography (eluent was PE / EA = 5:1) to obtain 2g of a white solid product with a yield of 60%. The product was characterized by nuclear magnetic resonance as follows:
[0047] 1 H NMR (400MHz, CDCl3) δ7.74(d,J=9.6Hz,1H),7.56(d,J=7.6Hz,1H),7.46-7.38(m,1H),7.33-7.14(m,7H),6.80(d,J=9.6Hz,1H),5.56(s,2H).
[0048] The above-mentioned embodiments merely express the implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the patent scope of the present invention. Any technical solution obtained in the form of equivalent replacement or equivalent transformation shall fall within the protection scope of the present invention.
Claims
1. A method for preparing quinolinone series compounds by dehydrogenation of dihydroquinolinone series compounds, characterized in that: include: Under the combined action of visible light irradiation, catalyst and oxidant, dihydroquinolinone series compounds undergo dehydrogenation reaction in organic solvent to generate corresponding quinolinone series compounds. The general structural formula of the dihydroquinolinone series compounds involved in this patent is: Where R 1 is one of methoxy, tert-butyl, hydrogen, bromine, trifluoromethyl, ester, and nitro, R 2 It is one of phenyl, benzyl and hydrogen.
2. The method for preparing quinolinone series compounds by dehydrogenation of dihydroquinolinone series compounds according to claim 1, characterized in that: The visible light is purple LED light with a wavelength of 415nm, and the lamp barrel power is 50W.
3. The method for preparing quinolinone series compounds by dehydrogenation of dihydroquinolinone series compounds according to claim 1, characterized in that: The catalyst is thioxanthone (TX).
4. The method for preparing quinolinone series compounds by dehydrogenation of dihydroquinolinone series compounds according to claim 1, characterized in that: The oxidant is tert-butyl benzoperoxoate.
5. The method for preparing quinolinone series compounds by dehydrogenation of dihydroquinolinone series compounds according to claim 1, characterized in that: The organic solvent is anhydrous dichloromethane (DCM).
6. A method for preparing quinolinone series compounds by dehydrogenation of dihydroquinolinone series compounds according to claims 1-5, characterized in that: The concentration of the dihydroquinolinone series substrates used was 0.02 M, thioxanthone was 5 mol%, tert-butylbenzoyl peroxide was 2 equivalents, and anhydrous dichloromethane was evaporated before use.
7. The method for preparing quinolinone series compounds by dehydrogenation of dihydroquinolinone series compounds according to claim 1, characterized in that: The reaction should be carried out under argon atmosphere at room temperature for 10 h.