CN116283761A - 3-alkenyl ketone substituted quinoline-2-ketone and green synthesis method thereof - Google Patents

3-alkenyl ketone substituted quinoline-2-ketone and green synthesis method thereof Download PDF

Info

Publication number
CN116283761A
CN116283761A CN202310090527.7A CN202310090527A CN116283761A CN 116283761 A CN116283761 A CN 116283761A CN 202310090527 A CN202310090527 A CN 202310090527A CN 116283761 A CN116283761 A CN 116283761A
Authority
CN
China
Prior art keywords
ketone
substituted quinoline
alkenyl
compound
reaction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202310090527.7A
Other languages
Chinese (zh)
Inventor
胡方芝
王保桂
李帅帅
王鹏
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Qingdao Agricultural University
Original Assignee
Qingdao Agricultural University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Qingdao Agricultural University filed Critical Qingdao Agricultural University
Priority to CN202310090527.7A priority Critical patent/CN116283761A/en
Publication of CN116283761A publication Critical patent/CN116283761A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a 3-alkenyl ketone substituted quinoline-2-ketone skeleton with biological activity and a green synthesis method thereof. The invention provides a structure of a 3-alkenyl ketone substituted quinoline-2-ketone bioactive framework. The structural formula of the 3-alkenyl ketone substituted quinoline-2-ketone bioactive framework is as follows:
Figure DDA0004070184110000011
wherein R is 2 Is any one of ethyl and n-propyl; r is R 3 Is any one of hydrogen atom, alkyl, halogen, trifluoromethyl and cyano. The invention provides a synthesis method thereof, which comprises the following steps: reacting an anthranilaldehyde compound with 4-hydroxy-6-methyl-2-pyrone under a certain condition to prepare the 3-alkenyl ketone substituted quinoline-2-ketone compound. The invention provides a method for synthesizing 3-alkenyl ketone substituted quinoline-2-ketone compounds with various structures.

Description

3-alkenyl ketone substituted quinoline-2-ketone and green synthesis method thereof
Technical Field
The invention relates to the technical field of pharmaceutical intermediates and chemical synthesis, in particular to a 3-alkenyl ketone substituted quinoline-2-ketone structure with bioactivity and a green synthesis method thereof.
Background
The quinoline-2-ketone and the derivative thereof are important heterocyclic compounds, have good biological activity, are widely applied in the field of medicine, and play an important role in the treatment of diseases such as cancer, atherosclerosis, schizophrenia, parkinson, alzheimer disease and the like. For example, aripiprazole is a novel atypical antipsychotic marketed in the united states in 2002 for the treatment of schizophrenia; rebamipide plays an important role in promoting regeneration of mucosal tissue, reducing tissue inflammatory reaction, enhancing mucosal barrier function, etc., and is a novel antiulcer agent marketed in japan in 1990; tipirfenib is a novel antitumor drug which can be used for treating myeloma and other cancers, and enters into clinical research of III phase in the United states at present, and the drugs are all quinoline-2-ketone derivatives. In view of the importance of the quinolin-2-one skeleton in the medical field, it is important to efficiently construct quinolin-2-one, especially a multi-functional substituted quinolin-2-one skeleton.
Figure BDA0004070184090000011
In 2014, the professor "shouyin plum" of the university of Henan industry used benzoyl formic acid and alkenyl amide as raw materials and silver nitrate as a catalyst, and constructed a 3, 4-dihydro-3-benzoyl-2 (1H) -quinolinone backbone by free radical reaction (J.org.chem., 2014,79,8094-8102). However, the reaction requires 2 equivalents of potassium thiosulfate as the oxidizing agent and requires a high temperature of 100 degrees to be carried out.
Figure BDA0004070184090000021
In 2019, luo Feixian, a national university institute of life and environmental sciences, reports that transition metal Pd/Cu synergistically catalyzes the aryl and intramolecular amination reaction of tandem hydrocarbon bonds, and a one-pot method is used to synthesize a 3, 4-dihydro-2 (1H) -quinolinone skeleton (Org. Lett.,2019,21,1668-1671). The reaction requires not only a relatively expensive metal catalyst, but also a reaction at 140 degrees.
Figure BDA0004070184090000022
Although the above reactions can synthesize quinolin-2-one frameworks with high efficiency, expensive metal catalysts or high temperature reaction conditions greatly limit the application of these reactions, especially limiting the further industrialization of pharmaceutical manufacturing enterprises.
Therefore, how to use cheap and easily available raw materials, green and mild reaction conditions to efficiently construct the quinoline-2-ketone skeleton, solves the problems existing in the current organic synthesis method, and synthesizes a series of quinoline-2-ketone derivatives is the problem to be solved at present.
Disclosure of Invention
The invention aims at overcoming the defects of the prior art and provides a 3-alkenyl ketone substituted quinoline-2-ketone structure with bioactivity and a green synthesis method thereof. The novel 3-alkenyl ketone substituted quinoline-2-ketone bioactive skeleton provided by the invention provides a novel model molecule for drug development. The synthesis method of the 3-alkenyl ketone substituted quinoline-2-ketone bioactive framework is based on the hydrogen migration process, the framework is efficiently synthesized in one step, the operation is simple, the efficiency is high, the practicability is high, the constructed framework contains various functional groups, and the later synthesis application of the framework is facilitated.
The technical scheme of the invention is realized as follows:
the 3-alkenyl ketone substituted quinoline-2-ketone bioactive framework has the structural formula shown as follows:
Figure BDA0004070184090000031
wherein R is 1 ，R 2 Is any one of ethyl and n-propyl; r is R 3 Is any one of hydrogen atom, alkyl, halogen, trifluoromethyl and cyano.
The compounds of the present invention may exist in the form of one or more stereoisomers. The various isomers include tautomers, geometric isomers, enantiomers, diastereomers and the like. These isomers and mixtures of these isomers are all within the scope of the present invention.
The invention also provides a synthesis method of the 3-alkenyl ketone substituted quinoline-2-ketone bioactive framework, and a synthetic process route diagram of the invention is shown in figure 1, and the synthesis method comprises the following steps:
uniformly mixing an anthranilate compound and 4-hydroxy-6-methyl-2-pyrone in a solvent, and reacting at 100-120 ℃ to prepare a 3-alkenyl ketone substituted quinoline-2-ketone compound;
wherein, the structural formula of the o-aminobenzaldehyde compound is shown as follows:
Figure BDA0004070184090000032
wherein R is 1 ，R 2 Is any one of ethyl and n-propyl; r is R 3 Is any one of hydrogen atom, alkyl, halogen, trifluoromethyl and cyano.
Wherein the structural formula of the 4-hydroxy-6-methyl-2-pyrone is as follows:
Figure BDA0004070184090000033
the reaction condition can be detected by thin layer chromatography, and the purification is carried out after the reaction is finished, so as to obtain the purified product of the 3-alkenyl ketone substituted quinoline-2-ketone compound.
The reaction process specifically comprises the following steps:
o-aminobenzaldehyde compound and 4-hydroxy-6-methyl-2-pyrone are subjected to Knoevenagel condensation reaction to form intermediate product electron-deficient olefin, the electron-deficient olefin is used as driving force to initiate intramolecular hydrogen migration to form an imine intermediate, then the imine intermediate containing amino and lactone is generated through dealkylation in the process of imine hydrolysis, and finally the final product 3-alkenyl ketone substituted quinoline-2-ketone is generated through intramolecular acylation reaction. The synthetic route is specifically as follows:
Figure BDA0004070184090000041
preferably, the synthesis process as described above is carried out at 120 ℃.
Preferably, the solvent used in the above reaction is green and pollution-free water. The solvent is used in the following amount: 10-20L of solvent is added to each mole of o-aminobenzaldehyde compound.
Preferably, the synthesis reaction does not adopt a catalyst, so that the product synthesis cost is effectively reduced.
The compounds of the present invention may exist in the form of one or more stereoisomers. The various isomers include geometric isomers. These isomers, including mixtures of these isomers, are within the scope of the present invention.
The beneficial effects of the invention are as follows:
1. according to the invention, under mild reaction conditions, the 3-alkenyl ketone substituted quinoline-2-ketone skeleton is efficiently synthesized by one-step reaction, and the technical scheme of the invention provides a convenient and concise synthesis method for the 3-alkenyl ketone substituted quinoline-2-ketone skeleton, so that the 3-alkenyl ketone substituted quinoline-2-ketone skeleton is efficiently constructed through a hydrogen migration process for the first time.
2. The invention develops a method for efficiently synthesizing 3-alkenyl ketone substituted quinoline-2-ketone compounds with multiple functional groups and multiple structures, provides a compound library with multiple structures and 3-alkenyl ketone substituted quinoline-2-ketone frameworks, and provides a novel model molecule for drug development.
3. The method has mild reaction conditions, the 3-alkenyl ketone substituted quinoline-2-ketone compound is synthesized in water through one-step reaction, the substrate universality is good, the substrate substituent can be an electron-withdrawing group or an electron-donating group, and the position of the substituent has no obvious influence on the reaction yield. The invention provides experimental basis for the efficient construction of 3-alkenyl ketone substituted quinoline-2-ketone skeleton with good biological activity, and has good practical significance and application value.
Drawings
FIG. 1 is a synthetic process scheme of the present invention.
Detailed Description
The following description of the embodiments of the present invention will clearly and fully describe the technical solutions of the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used in this specification includes any and all combinations of one or more of the associated listed items.
The experimental methods used in the following examples are all conventional methods unless otherwise specified; reagents, materials, instruments, etc. used in the examples described below are all commercially available unless otherwise specified; the reaction vessel used in the examples below was a 25mL thick-walled pressure-resistant tube.
Example 1
The embodiment provides a synthesis method of a 3-alkenyl ketone substituted quinoline-2-ketone bioactive framework, which comprises the following steps:
taking 0.1mmol of N-diethyl substituted o-aminobenzaldehyde compound in a reaction tube, sequentially adding 1mL of solvent, adding 0.12mmol of 4-hydroxy-6-methyl-2-pyrone, controlling the reaction temperature of the system, continuously stirring, and carrying out sample application tracking reaction through a thin layer chromatography plate until the raw materials are completely reacted. After the reaction is completed, separating and purifying by using a silica gel column, and rotary steaming the purified product to obtain a target product. The reaction formula is as follows:
Figure BDA0004070184090000061
2. according to the method, the following 10 parallel test groups are set, and different reaction conditions are respectively adopted, such as: different raw material proportions, different solvents, different solvent volumes, different temperatures. The specific settings for the different test groups are shown in Table 1:
TABLE 1 reaction yield of anthranilaldehyde with 4-hydroxy-6-methyl-2-pyruvic ketone under different conditions
Figure BDA0004070184090000062
From the above analysis of parallel test results, it can be seen that: when water is used as a solvent in the synthesis reaction, 10-20L of the solvent is added per mol of the o-aminobenzaldehyde compound, and the reaction can be carried out; when 10L of water is added to each mole of o-aminobenzaldehyde compound, the yield is highest; the reaction temperature is 120 ℃, and the yield is the highest. In addition, under the optimal reaction conditions, 30% of acetic acid or triethylamine is added as a catalyst in the reaction, the reaction yield is low,
in the following examples 2 to 10, reactions were carried out according to the procedure of example 1; in the reaction system, raw materials of o-aminobenzaldehyde compound and 4-hydroxy-6-methyl-2-pyrone are respectively 0.1mmol and 0.12mmol, water is used as a solvent, and the reaction is continuously stirred at 120 ℃ until the raw materials are completely reacted, so that corresponding target products are respectively obtained.
Example 2
Raw materials: n-diethyl-substituted anthranilic acid, 4-hydroxy-6-methyl-2-pyrone
The product is: the chemical formula: c (C) 15 H 17 NO 3
Molecular weight: 259.1208
Structural formula:
Figure BDA0004070184090000071
yield: 85%
1 H NMR(500MHz,CDCl 3 )δ15.04(s,1H),7.22–7.17(m,1H),7.13(t,J＝7.2Hz,1H),6.96(dd,J＝13.4,7.0Hz,2H),5.57(s,1H),4.02–3.87(m,2H),3.46(t,J＝6.8Hz,1H),3.25(dd,J＝15.6,7.7Hz,1H),2.97(dd,J＝15.6,5.8Hz,1H),1.95(s,3H),1.21(dd,J＝15.8,7.9Hz,3H). 13 C NMR(125MHz,CDCl 3 )δ191.5,188.5,166.9,138.6,128.4,127.8,124.7,123.2,114.7,99.8,50.7,37.9,28.2,23.9,12.6.HRMS(ESI)m/z:[M+Na] + calcd.for C 15 H 17 NNaO 3 :282.1101,found:282.1097.
Example 3
Raw materials: N-di-N-propyl substituted anthranilic acid, 4-hydroxy-6-methyl-2-pyrone
The product is: the chemical formula: c (C) 16 H 19 NO 3
Molecular weight: 273.1365
Structural formula:
Figure BDA0004070184090000072
yield: 65%
1 H NMR(500MHz,CDCl 3 )δ15.09(s,1H),7.24(d,J＝7.8Hz,1H),7.20(d,J＝7.2Hz,1H),7.01(dd,J＝19.4,7.7Hz,2H),5.64(s,1H),3.98–3.85(m,2H),3.55(t,J＝6.5Hz,1H),3.31(dt,J＝16.2,8.2Hz,1H),3.04(dd,J＝15.6,5.7Hz,1H),2.02(s,3H),1.69(dt,J＝15.6,7.7Hz,2H),0.97(t,J＝7.7Hz,3H). 13 CNMR(125MHz,CDCl 3 )δ191.6,188.3,167.1,138.7,128.4,127.7,124.8,123.2,114.9,99.8,50.8,44.3,28.2,23.9,20.4,11.3.HRMS(ESI)m/z:[M+H] + calcd.for C 16 H 20 NO 3 :274.1438,found:274.1434.
Example 4
Raw materials: n, N-diethyl-2-amino-6-fluorobenzaldehyde, 4-hydroxy-6-methyl-2-pyrone
The product is: the chemical formula: c (C) 15 H 16 FNO 3
Molecular weight: 277.1114
Structural formula:
Figure BDA0004070184090000081
yield: 63%
1 H NMR(500MHz,CDCl 3 )δ15.04(s,1H),7.21(dd,J＝14.8,7.3Hz,1H),6.80(t,J＝8.7Hz,2H),5.66(s,1H),4.00(m,2H),3.55(t,J＝6.2Hz,1H),3.40(dd,J＝16.1,7.0Hz,1H),3.02(dd,J＝16.1,5.6Hz,1H),2.03(s,3H),1.27(d,J＝7.7Hz,3H). 13 C NMR(125MHz,CDCl 3 )δ191.4,188.2,166.5,160.0(d,J＝242.5Hz),140.34(d,J＝6.4Hz),128.44(d,J＝9.5Hz),112.1(d,J＝21.3Hz),110.3(d,J＝8.8Hz),110.2(d,J＝11.2Hz),99.6,49.9,38.3,23.8,20.4(d,J＝4.1Hz),12.6.HRMS(ESI)m/z:[M+Na] + calcd.for C 15 H 16 FNNaO 3 :300.1006,found:300.1006.
Example 5
Raw materials: n, N-diethyl-2-amino-6-bromobenzaldehyde, 4-hydroxy-6-methyl-2-pyrone
The product is: the chemical formula: c (C) 15 H 16 BrNO 3
Molecular weight: 337.0314
Structural formula:
Figure BDA0004070184090000082
yield: 60 percent of
1 H NMR(500MHz,CDCl 3 )δ15.02(s,1H),7.27(s,1H),7.12(t,J＝7.7Hz,1H),6.97(d,J＝7.9Hz,1H),5.66(s,1H),3.99(m,2H),3.61–3.47(m,2H),3.14(d,J＝12.9Hz,1H),2.03(s,3H),1.30–1.24(m,3H). 13 C NMR(125MHz,CDCl 3 )δ191.2,188.2,166.5,139.9,128.6,127.4,124.8,124.1,114.0,99.7,50.2,38.4,27.9,23.9,12.6.HRMS(ESI)m/z:[M+H] + calcd.for C 15 H 17 BrNO 3 :338.0386,found:338.0389.
Example 6
Raw materials: n, N-diethyl-2-amino-4-chlorobenzaldehyde, 4-hydroxy-6-methyl-2-pyrone
The product is: the chemical formula: c (C) 15 H 16 ClNO 3
Molecular weight: 293.0819
Structural formula:
Figure BDA0004070184090000091
yield: 50 percent of
1 H NMR(500MHz,CDCl 3 )δ15.05(s,1H),7.12(d,J＝7.7Hz,1H),6.99(s,2H),5.63(s,1H),3.98(m,2H),3.54(s,1H),3.29(dd,J＝15.5,6.0Hz,1H),3.02(dd,J＝15.6,4.3Hz,1H),2.03(s,3H),1.29(t,J＝7.1Hz,3H). 13 C NMR(125MHz,CDCl 3 )δ191.3,188.3,166.7,139.7,133.4,129.4,123.1,123.0,115.0,99.6,50.5,38.1,27.6,23.8,12.5.HRMS(ESI)m/z:[M+H] + calcd.for C 15 H 17 ClNO 3 :294.0891,found:294.0895.
Example 7
Raw materials: n, N-diethyl-2-amino-4-methylbenzaldehyde, 4-hydroxy-6-methyl-2-pyrone
The product is: the chemical formula: c (C) 16 H 19 NO 3
Molecular weight: 273.1365
Structural formula:
Figure BDA0004070184090000092
yield: 62 percent of
1 H NMR(500MHz,CDCl 3 )δ15.11(s,1H),7.07(d,J＝7.1Hz,1H),6.83(d,J＝9.4Hz,2H),5.63(s,1H),3.99(m,2H),3.51(t,J＝6.4Hz,1H),3.27(dd,J＝15.6,7.4Hz,1H),3.00(dd,J＝15.5,5.5Hz,1H),2.36(s,3H),2.02(s,3H),1.29(t,J＝7.5Hz,3H). 13 C NMR(125MHz,CDCl 3 )δ191.7,188.5,166.9,138.5,137.6,128.2,123.9,121.6,115.4,99.8,50.9,37.9,27.9,23.9,21.6,12.7.HRMS(ESI)m/z:[M+Na] + calcd.for C 16 H 19 NNaO 3 :296.1257,found:296.1258.
Example 8
Raw materials: n, N-diethyl-2-amino-4-trifluoromethylbenzaldehyde, 4-hydroxy-6-methyl-2-pyrone
The product is: the chemical formula: c (C) 16 H 16 F 3 NO 3
Molecular weight: 327.1082
Structural formula:
Figure BDA0004070184090000101
(in the form of enol)
Yield: 72 percent of
1 H NMR(500MHz,DMSO)δ11.81(s,1H),7.31(dd,J＝8.5,1.8Hz,1H),7.24(d,J＝2.0Hz,1H),6.60(d,J＝8.5Hz,1H),6.08(d,J＝0.6Hz,1H),3.46(s,2H),3.13(d,J＝7.2Hz,2H),2.19(s,3H),1.23(t,J＝7.1Hz,3H). 13 C NMR(125MHz,DMSO)δ167.2,166.1,161.6,149.7,125.9(q,J＝268.8Hz),126.4(q,J＝3.8Hz),124.8(q,J＝3.8Hz),123.7,115.2(q,J＝31.3Hz),108.9,100.4,98.8,37.9,25.2,19.8,14.5.HRMS(ESI)m/z:[M+H] + calcd.for C 16 H 17 F 3 NO 3 :328.1155,found:328.1159.
Example 9
Raw materials: n, N-diethyl-2-amino-4-cyanobenzaldehyde, 4-hydroxy-6-methyl-2-pyrone
The product is: the chemical formula: c (C) 16 H 16 N 2 O 3
Molecular weight: 284.1161
Structural formula:
Figure BDA0004070184090000111
(in the form of enol)
Yield: 68%
1 H NMR(500MHz,DMSO)δ11.75(s,1H),7.06(d,J＝7.7Hz,1H),6.90(dd,J＝7.6,1.2Hz,1H),6.80(s,1H),6.08(s,1H),3.45(s,2H),3.11(q,J＝7.1Hz,2H),2.19(s,3H),1.22(t,J＝7.1Hz,3H). 13 C NMR(125MHz,DMSO)δ167.2,165.9,161.6,147.3,130.1,129.5,120.4,119.4,111.6,109.9,100.4,98.3,37.9,25.5,19.8,14.4.HRMS(ESI)m/z:[M+H] + calcd.for C 16 H 17 N 2 O 3 :285.1234,found:285.1222.
Example 10
Raw materials: n, N-diethyl-2-amino-5-cyanobenzaldehyde, 4-hydroxy-6-methyl-2-pyrone
The product is: the chemical formula: c (C) 16 H 16 N 2 O 3
Molecular weight: 284.1161
Structural formula:
Figure BDA0004070184090000112
(in the form of enol)
Yield: 67%
1 H NMR(500MHz,DMSO)δ11.83(s,1H),7.41(dd,J＝8.5,2.1Hz,1H),7.19(d,J＝2.0Hz,1H),6.58(d,J＝8.6Hz,1H),6.09(s,1H),3.41(s,2H),3.16(q,J＝7.1Hz,2H),2.20(s,3H),1.22(t,J＝7.2Hz,3H). 13 C NMR(125MHz,DMSO)δ167.3,165.9,161.8,150.3,132.7,132.3,124.1,121.3,109.5,100.4,98.3,95.8,37.7,25.0,19.8,14.4.HRMS(ESI)m/z:[M+H] + calcd.for C 16 H 17 N 2 O 3 :285.1234,found:285.1226.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.

Claims (7)

  1. The 3-alkenyl ketone substituted quinoline-2-ketone bioactive framework is characterized by having the following structural formula:
    Figure FDA0004070184080000011
    wherein R is 2 Is any one of ethyl and n-propyl; r is R 3 Is any one of hydrogen atom, alkyl, halogen, trifluoromethyl and cyano.
  2. 2. The method for synthesizing the 3-alkenyl ketone substituted quinoline-2-one bioactive skeleton according to claim 1, comprising the following steps:
    uniformly mixing an anthranilate compound and 4-hydroxy-6-methyl-2-pyrone in a solvent, and reacting at 100-120 ℃ to prepare a 3-alkenyl ketone substituted quinoline-2-ketone compound;
    wherein, the structural formula of the o-aminobenzaldehyde compound is shown as follows:
    Figure FDA0004070184080000012
    wherein R is 1 ，R 2 Is any one of ethyl and n-propyl; r is R 3 Is any one of hydrogen atom, alkyl, halogen, trifluoromethyl and cyano.
    Wherein the structural formula of the 4-hydroxy-6-methyl-2-pyrone is as follows:
    Figure FDA0004070184080000013
  3. 3. the synthetic method of claim 2 wherein the solvent is water, acetonitrile or tetrahydrofuran.
  4. 4. The synthesis method according to claim 2, wherein the molar ratio of the anthranilate compound to 4-hydroxy-6-methyl-2-pyrone is 1: (1-5).
  5. 5. The method of synthesis according to claim 2, wherein the solvent is used in an amount of: 10-20L of solvent is added to each mole of o-aminobenzaldehyde compound.
  6. 6. The synthetic method of claim 2 wherein the catalyst is added prior to the reaction, the catalyst being a bronsted or lewis acid.
  7. 7. The method according to claim 2 or 6, wherein the catalyst is used in an amount of 5 to 50mol%.
CN202310090527.7A 2023-02-02 2023-02-02 3-alkenyl ketone substituted quinoline-2-ketone and green synthesis method thereof Pending CN116283761A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202310090527.7A CN116283761A (en) 2023-02-02 2023-02-02 3-alkenyl ketone substituted quinoline-2-ketone and green synthesis method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202310090527.7A CN116283761A (en) 2023-02-02 2023-02-02 3-alkenyl ketone substituted quinoline-2-ketone and green synthesis method thereof

Publications (1)

Publication Number Publication Date
CN116283761A true CN116283761A (en) 2023-06-23

Family

ID=86777093

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202310090527.7A Pending CN116283761A (en) 2023-02-02 2023-02-02 3-alkenyl ketone substituted quinoline-2-ketone and green synthesis method thereof

Country Status (1)

Country Link
CN (1) CN116283761A (en)

Similar Documents

Publication Publication Date Title
CN110143918B (en) 3, 4-dihydro-3- (2-hydroxybenzoyl) -2(1H) -quinolinone active skeleton, synthetic method and application
CN116283761A (en) 3-alkenyl ketone substituted quinoline-2-ketone and green synthesis method thereof
CN110204533B (en) Preparation method of 4- (isochromen-1-yl) isoquinoline derivative
CN106749235B (en) The preparation method of poly-substituted quinoline and azole derivatives
JPH01221374A (en) Production of 4-oxo-1-benzopyran-2-carboxylic acid derivative having optical activity, intermediate for synthesizing said derivative and production of said intermediate
CN105820174A (en) Polysubstituted thienoindole derivative and preparation method thereof
CN104788396A (en) Preparation method of N-substituted oxazolone polymer derivatives
CN113651813A (en) 2, 3-dihydroquinoline-4-ketone bioactive skeleton and synthesis method and application thereof
CN113429409A (en) Sulfur-containing polysubstituted indolizine compound and preparation method thereof
CN112500419A (en) Epoxy fused 2-methylene pyrrolidine compound and preparation method thereof
CN111471041B (en) Synthetic method of oxazolidinone antibacterial drug intermediate
CN109748809B (en) Method for synthesizing 2-substituted amino-1, 4-naphthoquinone derivative
CN107188909B (en) Method for synthesizing indole-substituted or ferrocene-substituted azaarene
CN117185999A (en) Green synthesis method of 3, 4-dihydro-2 (1H) -quinolinone bioactive framework
CN115974781A (en) Green synthesis method of beta-amino acid derivative active skeleton
CN111892582B (en) Preparation method of benzofuran coumarin compound
CN115477627B (en) Polysubstituted 2-furanone compound and synthesis method thereof
CN114634427B (en) Preparation method of indeno polycyclic compound containing spiro
CN113845481B (en) Synthesis method of 4, 4-dimethyl-4, 5-dihydropyridazin-3-one
CN113636968B (en) Synthetic method of 3-acyl pyrrole compound
CN116444534A (en) Fluoroalcohol-promoted [5+1] dearomatization reaction
CN110467613B (en) Reaction method for alkylation of imide cation intramolecular amide by nickel catalysis
CN116003369A (en) 3-spirohexenone substituted chroman structure and synthesis method thereof
CN114605437A (en) Synthesis process for preparing three telaprevir medicaments by continuous one-pot method
CN117402119A (en) Preparation method of trifluoromethyl substituted dihydroquinoxaline compound

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination