CN115232070B - Quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom, and preparation method and application thereof - Google Patents
Quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom, and preparation method and application thereof Download PDFInfo
- Publication number
- CN115232070B CN115232070B CN202210783046.XA CN202210783046A CN115232070B CN 115232070 B CN115232070 B CN 115232070B CN 202210783046 A CN202210783046 A CN 202210783046A CN 115232070 B CN115232070 B CN 115232070B
- Authority
- CN
- China
- Prior art keywords
- quinolin
- oxo
- nitrogen atom
- group
- solvent
- 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.)
- Active
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
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
- A01N43/42—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- Plant Pathology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Health & Medical Sciences (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention aims to provide a quinolinone alkaloid derivative containing an acylhydrazone group on a 1-position nitrogen atom, a preparation method thereof and application thereof in the aspect of controlling plant viruses, and belongs to the technical field of pesticides. Firstly, reacting 1H-quinolin-4-one with alpha-bromoethyl acetate in a solvent in the presence of a base at room temperature to form (oxo-4H-quinolin-1-yl) -ethyl acetate; secondly, reacting (oxo-4H-quinolin-1-yl) -ethyl acetate with water and hydrazine in a solvent to form (4-oxo-4H-quinolin-1-yl) -acethydrazide; thirdly, reacting (4-oxo-4H-quinolin-1-yl) -acethydrazide with aldehyde in a solvent to form a quinolinone alkaloid derivative having an acylhydrazone group on the 1-position nitrogen atom. The compound of the invention shows the activity of resisting the tobacco mosaic virus, and the activity of resisting the tobacco mosaic virus of part of the compounds is higher than that of ribavirin.
Description
Technical Field
The invention belongs to the technical field of pesticides, and particularly relates to a quinolinone alkaloid derivative containing an acylhydrazone group on a 1-position nitrogen atom, and a preparation method and application thereof.
Background
The plant virus has more than 900, can greatly reduce the yield of grains and cause huge economic loss. Tobacco mosaic virus is an RNA virus capable of infecting 260 plants of 38 families such as tomatoes, potatoes, peppers, etc., causing serious economic losses (Huang, y.q. et al j. Agric. Food chem. 2018, 66, 8253-8261). At present, common tobacco mosaic virus inhibitors are ningnanmycin and ribavirin. However, both plant virus inhibitors are not environmentally friendly and the antiviral activity is to be improved. At present, the literature reports that various natural product derivatives have anti-tobacco mosaic virus activity (Yang, s.et al molecular, 2021, 26, 383.zou, j.b. et al j.agric.food chem., 2020, 68, 15015-15026). However, quinolinone alkaloid derivatives have been rarely studied as tobacco mosaic virus inhibitors.
Disclosure of Invention
The invention aims to provide a quinolinone alkaloid derivative containing an acylhydrazone group on a 1-position nitrogen atom, a preparation method thereof and application thereof in the aspect of preventing and treating plant viruses. The quinolinone alkaloid derivative containing the acylhydrazone structure on the 1-position nitrogen atom shows good activity of resisting and treating the tobacco mosaic virus.
The invention adopts the following technical scheme:
a quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom has a structural general formula shown in formula (I):
Further, the substituent of the substituted phenyl group includes any one or both of hydrogen, hydroxyl, halogen atom, cyano, nitro, ester group, fluorine, trifluoromethyl, trifluoromethoxy, 1-5 carbon hydrocarbon group and 1-6 carbon alkoxy group, and contains 2 to 3 of the above substituents.
Further, a quinolinone alkaloid derivative containing an acylhydrazone group on the 1-position nitrogen atom includes (4-oxo-4H-quinolin-1-yl) -acetylbenzylidene hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-methyl-benzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-tert-butylbenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-phenylbenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (3-phenoxybenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-methylthiobenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-methylsulfonylbenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-pyrazol-1-benzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-fluoro-4-benzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-chlorobenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-bromobenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-nitrobenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-trifluoromethyl benzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-dimethylaminobenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (2-nitrobenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (pyridin-3-ylmethylene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (furan-2-ylmethylene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (thiophen-2-ylidene) acetyl (4-oxo-4-quinolin-1-yl) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (indol-2-ylmethylene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (benzofuran-3-ylmethylene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (9-ethyl-9H-carbazol-3-ylmethylene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (3, 4-dimethoxybenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (5-bromo-2-methoxybenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (3, 5-dibromo-4-hydroxybenzylidene) hydrazine.
A preparation method of quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom comprises the following steps:
firstly, reacting 1H-quinolin-4-one with alpha-bromoethyl acetate in a solvent in the presence of a base at room temperature to form (oxo-4H-quinolin-1-yl) -ethyl acetate;
secondly, reacting (oxo-4H-quinolin-1-yl) -ethyl acetate with water and hydrazine in a solvent to form (4-oxo-4H-quinolin-1-yl) -acethydrazide;
thirdly, reacting (4-oxo-4H-quinolin-1-yl) -acethydrazide with aldehyde in a solvent to form a quinolinone alkaloid derivative having an acylhydrazone group on the 1-position nitrogen atom.
Further, the solvent in the first step comprises N, N-dimethylformamide.
Further, the base in the first step includes any one of cesium carbonate, sodium carbonate and potassium carbonate.
Further, the solvent in the second step comprises methanol.
Further, the reaction temperature in the second step is 65 ℃.
Further, the solvent in the third step includes any one of methanol, ethanol and acetonitrile.
Further, the temperature of the reaction in the third step is 20-130 ℃.
Further, the aldehyde in the third step includes any one of benzaldehyde, 4-methylbenzaldehyde, 4-t-butylbenzaldehyde, 4-phenylbenzaldehyde, 3-methoxybenzaldehyde, 4-methylthiobenzaldehyde, 4-methylsulfonylbenzaldehyde, pyrazole-1-carbaldehyde, 4-fluorobenzaldehyde, 4-chlorobenzaldehyde, 4-bromobenzaldehyde, 4-nitrobenzaldehyde, 4-trifluoromethylbenzaldehyde, 4-dimethylaminobenzaldehyde, 2-nitrobenzaldehyde, pyridine-3-carbaldehyde, furan-2-carbaldehyde, thiophene-2-carbaldehyde, thiazole-4-carbaldehyde, indole-2-carbaldehyde, benzofuran-3-carbaldehyde, 9-ethyl-9H-carbazol-3-carbaldehyde, 3, 4-dimethoxybenzaldehyde, 5-bromo-2-methoxybenzaldehyde and 3, 5-dibromo-4-hydroxybenzaldehyde.
A quinolinone alkaloid derivative containing an acylhydrazone group on a 1-position nitrogen atom is applied to prevention and treatment of tobacco mosaic virus.
The beneficial effects of the invention are as follows:
the compound of the invention shows the activity of resisting the tobacco mosaic virus, and the activity of resisting the tobacco mosaic virus of part of the compounds is higher than that of ribavirin.
Drawings
FIG. 1 is a flow chart of the preparation method of the invention.
Detailed Description
The following examples and green test results are intended to further illustrate the invention and are not meant to limit the invention.
As shown in fig. 1:
in the first step, preparation of compound b:
DMF (100 mL), compound a (4.35 g,30 mmol), K were added sequentially in a 250 mL single-necked flask 2 CO 3 (6.22 g,45 mmol) and ethyl bromoacetate (8.02 g,48 mmol). The reaction was stirred at room temperature for 12 hours and TLC monitored the reaction was complete. Water (100 mL) was added to the reaction mixture, followed by CH 2 Cl 2 The extraction was performed three times and the organic phases were combined. The organic phase was washed three times with saturated brine (200 mL), dried over anhydrous sodium sulfate, spin-distilled to remove the solvent, and subjected to column chromatography (eluent: CH) 2 Cl 2 /CH 3 Oh=20:1) to give b (5.364 g, 77.4%) as a white solid. Melting point 157 o C。 1 H NMR (400Hz，CDCl 3 ) 8.45 (d，J = 8.0 Hz，1H)，7.66 - 7.62 (m，1H)，7.47 (d，J = 7.6 Hz，1H)，7.40 - 7.37 (m，1H)，7.19 (d，J = 8.4 Hz，1H)，6.29 (d，J = 7.6 Hz，1H)，4.77 (s，2H)，4.24 (q，J = 7.2 Hz，2H)，1.25 (t，J = 7.2 Hz，3H). 13 C NMR (100Hz，CDCl 3 ) 178.4，167.2，143.7，140.2，132.5，127.3，127.1，124.0，114.6，110.8，62.4，54.0，14.1. ESI-HRMS(m/z):Calcd. for C 13 H 14 NO 3 [M+H] + 232.0974；found 232.0965。
In the second step, preparation of compound c:
methanol (300 mL), compound b (2.31 g,10 mmol) and hydrazine hydrate (5 g,80%,100 mmol) were added sequentially to a 500 mL single-port flask, and the reaction was refluxed for 8 hours, followed by TLC to monitor the completion of the reaction. The reaction solution was cooled to room temperature, and most of the methanol was removed by rotary evaporation until a large amount of white solid was precipitated. Filtration under reduced pressure afforded c (1.775 g, 81.8%) as a white solid, melting point 240 o C。 1 H NMR (400Hz，DMSO-d 6 ) 9.53 (s，1H)，8.17 (d，J = 7.2 Hz，1H)，7.92 (d，J = 7.6 Hz，1H)，7.72 - 7.68 (m，1H)，7.44 (d，J = 8.8 Hz，1H)，7.39 - 7.35 (m，1H)，6.07 (d，J = 7.6 Hz，1H)，4.86 (s，2H)，4.36 (s，2H). 13 C NMR (100Hz，DMSO-d 6 ) 176.5，166.0，145.7，140.3，132.0，126.5，125.7，123.3，116.0，108.7，52.8. ESI-HRMS(m/z):Calcd. for C 11 H 12 N 3 O 2 [M+H] + 218.0930；found 218.0924。
Third step, quinolinone alkaloid derivative (I) containing acylhydrazone group on 1-position nitrogen atom 1 - I 25 ) Is prepared from the following steps:
example 1
(4-oxo-4H-quinolin-1-yl) -acetylbenzylidene hydrazine (I) 1 ) Is a benzaldehyde.
Methanol (50 mL), compound c (0.217 g,1 mmol), benzaldehyde d were added sequentially to a 100mL round bottom flask 1 (0.106 g,1 mmol) and the reaction was refluxed for 12 hours and monitored by TLC. The reaction solution was cooled to room temperature, and most of the methanol was removed by rotary evaporation until a large amount of white solid was precipitated. Filtering under reduced pressure to obtain yellow solid I 1 (0.2308 g, 75.7%). Melting point 260 ℃. 1 H NMR (400Hz，DMSO-d 6 ) 11.93 and 11.84 (s，1H)，8.19 (dd，J = 8.0，2.0 Hz，1H)，8.10 (s，1H)，8.01 - 7.97 (m，1H)，7.81 - 7.78 (m，2H)，7.73 - 7.65 (m，2H)，7.50 - 7.44 (m，3H)，7.39 - 7.35 (m，1H)，6.12 - 6.09 (m，1H)，5.55 (s，2H). 13 C NMR (100Hz，DMSO-d 6 ) 176.5，168.3 and 163.9，147.7 and 144.3，145.7 and 145.5，140.7，133.9，131.9，130.1，128.8，127.1，126.4，125.7 and 125.5，123.2 and 123.1，116.5 and 116.1，108.8，53.2 and 52.8. ESI-HRMS(m/z):Calcd.for C 18 H 16 N 3 O 2 [M+H] + 306.1237; found 306.1239。
Example 2
(4-oxo-4H-quinolin-1-yl) -acetyl (4-methyl-benzylidene) hydrazine (I) 2 ) The aldehyde is 4-methylbenzaldehyde.
0.229g of pale yellow solid was obtained in 71.8% yield. Melting point 232 ℃. 1 H NMR (400Hz，DMSO-d 6 ) 11.88 and 11.79 (s，1H)，8.23 and 8.06 (s，1H)，8.19 (d，J = 8.0 Hz，1H)，8.01 - 7.97 (m，1H)，7.73 - 7.59 (m，3H)，7.50 - 7.35 (m，2H)，7.29 - 7.24 (m，2H)，6.12 - 6.09 (m，1H)，5.53 and 5.06 (s，2H)，2.35 and 2.33 (s，3H). 13 C NMR (100Hz，DMSO-d 6 ) 176.7，168.2 and 163.3，147.8 and 144.5，145.8 and 145.6，140.7，140.0，132.2 and 132.0，131.2，129.5，127.2 and 127.1，126.4，125.6，123.4 and 123.2，116.6，108.9，53.3 and 52.9，21.1. ESI-HRMS(m/z):Calcd. for C 19 H 18 N 3 O 2 [M+H] + 320.1399；found 320.1396。
Example 3
(4-oxo-4H-quinolin-1-yl) -acetyl (4-t-butylbenzylidene) hydrazine (I) 3 ) The aldehyde is 4-tert-butylbenzaldehyde.
0.2266g of pale yellow solid was found to be 62.8% yield. Melting point of more than 300 o C。 1 H NMR (400Hz, DMSO-d 6 ) 11.87 and 11.80 (s, 1H), 8.24 and 8.07 (s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.01 and 7.98 (d, J = 7.6 Hz, 1H), 7.73 - 7.70 (m, 2H), 7.67 - 7.63 (m, 1H), 7.50 -7.48 (m, 2H), 7.46 -7.35 (m, 2H), 6.12 - 6.09 (m, 1H), 5.52 and 5.06 (s, 2H), 1.30 and 1.28 (s, 9H). 13 C NMR (100Hz, DMSO-d 6 ) 176.6, 168.1 and 163.2, 153.1 and 153.0, 147.7 and 144.4, 145.8 and 145.6, 140.7 and 140.5, 132.1 and 132.0, 131.2, 127.0 and 126.9, 126.4 and 125.6, 123.4 and 123.2, 116.4 and 116.1, 108.8, 53.3 and 52.8, 34.6, 31.0. ESI-HRMS(m/z):Calcd. for C 22 H 24 N 3 O 2 [M+H] + 362.1869; found 362.1864。
Example 4
(4-oxo-4H-quinolin-1-yl) -acetyl (4-phenylbenzylidene) hydrazine (I 4 ) The aldehyde is 4-phenylbenzaldehyde.
0.3509g of white solid was obtained in 92.1% yield. Melting point 260 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.97 and 11.89 (s, 0.75H), 8.32 and 8.14 (s, 0.24H), 8.20 (d, J = 7.6 Hz, 1H), 8.02 (d, J = 8.0 Hz,1H), 7.90 - 7.88 and 7.82 - 7.66 (m, 7H), 7.51 -7.46 (m, 3H), 7.42 - 7.35 (m, 2H), 6.13 -6.10 (m, 1H), 5.57 and 5.09 (s, 1H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.3 and 163.4, 147.3 and 144.0, 145.8 and 145.6, 144.0, 141.6, 140.7 and 140.5, 139.3, 133.0, 132.0, 129.1, 128.0, 127.8 and 127.7, 127.0, 126.7 and 126.4, 125.7 and 125.6, 123.4 and 123.2, 116.6 and 116.2, 108.9, 53.3 and 52.9. ESI-HRMS(m/z):Calcd. for C 24 H 20 N 3 O 2 [M+H] + 382.1556; found 382.1554。
Example 5
(4-oxo-4H-quinolin-1-yl) -acetyl (3-phenoxybenzal) hydrazine (I) 5 ) The aldehyde is 3-methoxybenzaldehyde.
0.2344g of yellow solid was found to be 70.0% yield. Melting Point 202 o C。 1 H NMR (400Hz, DMSO-d 6 ) 12.01 and 11.90 (s, 1H), 8.26 and 8.07 (s, 1H), 8.21 (d, J = 8.0 Hz, 1H), 8.02 (d, J =7.6 Hz, 1H), 7.72 - 7.66 (m, 1H), 7.47 - 7.35 (m, 5H), 7.05 - 7.01 (m, 1H), 6.14 - 6.10 (m, 1H), 5.57 and 5.09 (s, 2H), 3.82 and 3.79 (s, 3H). 13 C NMR (100Hz, DMSO-d 6 ) 177.1, 168.8 and 163.9, 160.0, 148.1 and 144.7, 146.3 and 146.1, 141.4 and 140.9, 135.8, 132.6 and 132.4, 130.4, 126.9, 126.2 and 126.0, 123.9 and 123.7, 120.5 and 120.3, 117.0 and 116.9, 116.6, 112.1 and 112.0, 109.3, 55.7 and 55.6, 53.8 and 53.3. ESI-HRMS(m/z):Calcd. for C 19 H 18 N 3 O 3 [M+H] + 336.1348; found 336.1343。
Example 6
(4-oxo-4H-quinolin-1-yl) -acetyl (4-methylthiobenzylidene) hydrazine (I 6 ) Is 4-methylthiobenzaldehyde.
0.1436g of yellow solid was found to be 42.8% yield. Melting point 265 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.90 and 11.83 (s, 1H), 8.22 and 8.05 (s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.73 - 7.63 (m, 3H),7.50 -7.44 (m, 1H), 7.40 -7.30 (m, 3H), 6.12 -6.09 (m, 1H), 5.33 and 5.07 (s, 2H), 2.51 and 2.50 (s, 3H). 13 C NMR (100Hz, DMSO-d 6 ) 177.1, 168.6 and 163.7, 147.8 and 144.5, 146.2 and 146.1, 141.8 and 141.5, 141.2 and 140.9, 132.6 and 132.4, 130.8, 128.1 and 128.0, 126.9, 126.2 and 126.1, 123.8 and 123.7, 117.0 and 116.6, 109.3, 53.8 and 53.3, 14.7 and 14.6. ESI-HRMS(m/z):Calcd. for C 19 H 18 N 3 O 2 S [M+H] + 352.1120; found 352.1117。
Example 7
(4-oxo-4H-quinolin-1-yl) -acetyl (4-methanesulfonyl benzylidene) hydrazine (I 7 ) Is 4-methanesulfonyl benzaldehyde.
0.2884g of yellow solid was found to be 75.3% yield. The melting point is greater than 300 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.18 and 12.09 (s, 1H), 8.35 and 8.17(s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.07 - 7.96 (m, 5H), 7.73 -7.65 (m, 1H), 7.51 -7.46 (m, 1H), 7.40 - 7.35 (m, 1H), 6.11 (d, J = 7.6 Hz, 1H), 5.59 and 5.12 (s, 2H). 3.27 and 3.25 (s, 3H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.7 and 163.8, 145.9 and 142.6, 145.8 and 145.6, 141.6 and 141.4, 140.7 and 140.5, 138.7, 132.2 and 132.0, 127.8, 127.5, 126.4, 125.8 and 125.6, 123.5 and 123.3, 116.6 and 116.2, 108.9, 53.3 and 52.9, 43.4. ESI-HRMS(m/z):Calcd. for C 19 H 18 N 3 O 4 S [M+H] + 384.1018; found 384.1015。
Example 8
(4-oxo-4H-quinoline)-1-yl) -acetyl (4-pyrazol-1-yl-benzylidene) hydrazine (I 8 ) The aldehyde is pyrazole-1-formaldehyde.
White solid 0.26g, yield 70.1%. Melting point 284 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.98 and 11.89 (s, 1H), 8.60 and 8.58 (s, 1H), 8.30 and 7.80 (s, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.12 (s, 1H), 8.01 (d, J = 7.6 Hz, 1H), 7.97 - 7.91 and 7.85 -7.82 (m, 4H), 7.74 - 7.66 (m, 1H), 7.51 - 7.46 (m, 1H), 7.41 -7.35 (m, 1H), 6.59 (s, 1H), 6.11 (d, J = 7.2 Hz, 1H), 5.58 and 5.09 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.3 and 163.4, 146.9 and 146.3, 145.8 and 145.6, 141.5, 140.8 and 140.7, 140.6 and 140.5, 132.2 and 132.0, 131.7 and 131.6, 128.5 and 128.4, 128.0 and 127.9, 126.4, 125.8 and 125.6, 123.4 and 123.2, 118.5 and 118.4, 116.6 and 116.2, 108.9, 108.3, 53.3 and 52.9. ESI-HRMS(m/z):Calcd. for C 21 H 18 N 5 O 2 [M+H] + 372.1461; found 372.1457。
Example 9
(4-oxo-4H-quinolin-1-yl) -acetyl (4-fluorobenzylidene) hydrazine (I 9 ) The aldehyde is 4-fluorobenzaldehyde.
0.2515g of yellow solid was found to be 77.9% yield. Melting point 280 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.93 and 11.85 (s, 1H), 8.27 and 8.03 (s, 1H), 8.20 - 8.17 (m, 1H), 8.00 -7.97 (m, 1H), 7.88 - 7.65 (m, 3H), 7.49 - 7.27 (m, 4H), 6.11 - 6.08 (m, 1H), 5.54 and 5.06 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.6 and 164.3, 168.3 and 163.3, 146.6 and 143.2, 145.7 and 145.5, 140.7 and 139.6, 132.1 and 132.0, 129.3, 129.2, 126.4, 125.7 and 125.5, 123.3 and 123.1, 116.5, 116.1 and 116.0, 115.7, 108.8, 53.3 and 52.8. ESI-HRMS(m/z):Calcd. for C 18 H 15 FN 3 O 2 [M+H] + 324.1148; found 324.1145。
Example 10
(4-oxo-4H-quinolin-1-yl) -acetyl (4-chlorobenzyl) hydrazine (I 10 ) The aldehyde is 4-chlorobenzaldehyde.
Yellow solid 0.179g, yield 52.8%. Melting point 260 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.03 and 11.92 (s, 1H), 8.27 and 8.08 (s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.01 - 7.97 (m, 1H), 7.83 and 7.74 (m, 2H), 7.69 - 7.64 (m, 1H), 7.55 - 7.44 (m, 3H), 7.40 - 7.34 (m, 1H), 6.12 -6.09 (m, 1H), 5.55 and 5.08 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7 and 176.6, 168.4 and 163.5, 146.5 and 143.1, 145.8 and 145.6, 140.7 and 140.5, 134.8 and 134.6, 132.9, 132.1 and 132.0, 129.0 and 128.9, 128.8 and 128.7, 126.5 and 126.4, 125.7 and 125.6, 123.4 and 123.2, 116.6 and 116.2, 108.9, 53.3 and 52.8. ESI-HRMS(m/z):Calcd. for C 18 H 15 ClN 3 O 2 [M+H] + 340.0853; found 340.0849。
Example 11
(4-oxo-4H-quinolin-1-yl) -acetyl (4-bromobenzylidene) hydrazine (I) 11 ) The aldehyde is 4-bromobenzaldehyde.
0.2845g of yellow solid was found to be 74.1% yield. Melting point 282 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.00 and 11.91 (s, 1H), 8.25 and 8.06 (s, 1H), 8.21-8.17 (m, 1H), 8.00-7.97 (m, 1H), 7.77 -7.45 (m, 2H), 7.68 - 7.65 (m, 3H), 7.49 - 7.44 (m, 1H), 7.40 - 7.35 (m, 1H), 6.12 - 6.07 (m, 1H), 5.55 and 5.07 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.5, 168.4 and 163.4, 146.3 and 143.1, 145.7 and 145.5, 140.6, 133.2, 131.8 and 131.7, 128.9, 126.4, 125.5, 123.3, 123.1, 116.5, 108.8, 53.2 and 52.8. ESI-HRMS(m/z):Calcd. for C 18 H 15 BrN 3 O 2 [M+H] + 384.0348; found 384.0345。
Example 12
(4-oxo-4H-quinolin-1-yl) -acetyl (4-nitrobenzyl) hydrazine (I) 12 ) The aldehyde is 4-nitrobenzaldehyde.
0.3148g of pale yellow solid was obtained in 90.0% yield. Melting point 292 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.26 and 12.15 (s, 1H), 8.32 - 8.28 (m, 2H), 8.20 - 8.17 (m, 2H), 8.08 - 7.97 (m, 3H), 7.71 - 7.65 (m, 1H), 7.50 - 7.47 (m, 1H), 7.41 - 7.35 (m, 1H), 6.12 - 6.10 (m, 1H), 5.60 and 5.12 (s, 0.42H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.8 and 164.8, 148.0 and 147.9, 145.8 and 145.6, 145.4 and 142.0, 140.7, 140.2, 132.8 and 132.0, 128.2 and 128.1, 126.4, 125.8 and 125.6, 124.0, 123.4 and 123.3, 116.6 and 116.2, 108.9, 53.3 and 52.9. ESI-HRMS(m/z):Calcd. for C 18 H 15 N 4 O 4 [M+H] + 351.1093; found 351.1087。
Example 13
(4-oxo-4H-quinolin-1-yl) -acetyl (4-trifluoromethylbenzylidene) hydrazine (I) 13 ) Is 4-trifluoromethyl benzaldehyde.
0.2582g of yellow solid was found to be 69.2% yield. Melting point 270 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.14 and 12.05 (s, 1H), 8.35 and 8.16 (s, 1H), 8.21- 8.18 (m, 1H), 8.03- 7.92 (m, 3H), 7.84 -7.80 (m, 2H), 7.69 -7.65 (m, 1H), 7.50 - 7.46 (m, 1H), 7.39 -7.35 (m, 1H), 6.13 - 6.10 (m, 1H), 5.58 and 5.11 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.7 and 163.7, 145.8 and 145.6, 142.7, 140.7 and 140.5, 137.9, 132.2 and 132.0, 127.8 and 127.7, 126.4, 125.7, 125.6, 125.5, 123.4 and 123.2, 116.6 and 116.2, 108.9, 53.3 and 52.8. ESI-HRMS(m/z):Calcd. for C 19 H 15 F 3 N 3 O 2 [M+H] + 374.1116; found 374.1110。
Example 14
(4-oxo-4H-quinolin-1-yl) -acetyl (4-dimethylaminobenzylidene) hydrazine (I) 14 ) The aldehyde is 4-dimethylaminobenzaldehyde.
Orange solid 0.255g, 73.3% yield. Melting point 160 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.65 and 11.57 (s, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.11 and 7.95(s, 1H), 8.01- 7.96 (m, 1H), 7.69 - 7.57 (m, 3H), 7.52 - 7.34 (m, 2H), 6.77 -6.72 (m, 2H), 6.11 - 6.08 (m, 1H), 5.48 and 5.02 (s, 2H), 2.97 and 2.96 (s, 6H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 167.6 and 162.6, 151.7 and 151.5, 148.5 and 145.3, 145.9 and 145.7, 140.7 and 140.5, 132.2 and 132.0, 128.6, 128.4, 126.5 and 126.4, 125.7 and 125.6, 123.4 and 123.2, 121.2 and 121.1, 116.5 and 116.2, 111.8, 108.8 and 108.7, 53.4 and 52.8, 39.8. ESI-HRMS(m/z):Calcd. for C 20 H 21 N 4 O 2 [M+H] + 349.1665; found 349.1660。
Example 15
(4-oxo-4H-quinolin-1-yl) -acetyl (2-nitrobenzyl) hydrazine (I) 15 ) The aldehyde is 2-nitrobenzaldehyde.
0.278g of pale yellow solid was obtained in 79.4% yield. Melting point 250 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.29 and 12.14 (s, 1H), 8.49 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.20 (d, J = 7.6 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.85 - 7.82 (m, 1H), 7.72 - 7.67 (m, 2H), 7.52 - 7.47 (m, 1H), 7.40 - 7.35 (m, 1H), 6.13 - 6.10 (m, 1H), 5.57 and 5.12 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.6 and 163.8, 148.2 and 148.1, 145.7 and 145.5, 143.4 and 140.0, 140.7 and 140.5, 133.9 and 133.6, 133.2 and 132.0, 130.9 and 130.8, 128.6 and 128.5, 128.2 and 128.1, 126.4, 125.7 and 125.6, 124.8 and 124.6, 123.4 and 123.3, 116.5 and 116.2, 108.9, 53.2 and 52.8.ESI-HRMS(m/z):Calcd. for C 18 H 15 N 4 O 4 [M+H] + 351.1093; found 351.1090。
Example 16
(4-oxo-4H-quinolin-1-yl) -acetyl (pyridin-3-ylmethylene) hydrazine (I) 16 ) Is pyridine-3-formaldehyde.
0.2381g of yellow solid was found to be 77.8% yield. Melting point 260 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.09 and 12.01 (s, 1H), 8.97 and 8.86 (s, 1H), 8.63 - 8.60 (m, 1H), 8.33 - 8.18 (m, 2H), 8.13 (s, 1H), 7.99 (d, J = 7.60 Hz, 1H), 7.69 - 7.65 (m, 1H), 7.51 - 7.35 (m, 3H), 6.10 (d, J = 7.60 Hz, 1H), 5.58 and 5.09 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.6 and 163.6, 150.9 and 150.7, 148.9 and 148.7, 145.8 and 145.6, 145.2 and 141.7, 140.7 and 140.5, 133.8 and 133.6, 132.2 and 132.0, 129.9, 126.4, 125.8 and 125.6, 124.1 and 124.0, 123.5 and 123.3, 116.6 and 116.2, 108.9, 53.3 and 52.9. ESI-HRMS(m/z):Calcd. for C 17 H 15 N 4 O 2 [M+H] + 307.1195; found 307.1190。
Example 17
(4-oxo-4H-quinolin-1-yl) -acetyl (furan-2-ylmethylene) hydrazine (I 17 ) The aldehyde is furan-2-formaldehyde.
The earthy yellow solid is 0.281g and the yield is 95.3 percent. Melting point 270 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.90 and 11.82 (s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.16 and 7.99 (s, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.87 and 7.83 (s, 1H), 7.71 - 7.64 (m, 1H), 7.49 - 7.34 (m, 2H), 6.98 - 6.95 (d, J = 3.6 Hz, 1H), 6.66 - 6.65 and 6.63 - 6.62 (m, 1H), 6.13 - 6.10 (m, 1H), 5.45 and 5.07(s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.0 and 163.3, 148.9, 145.8 and 145.7, 145.4 and 145.2, 140.7 and 140.5, 138.2 and 134.6, 132.1 and 132.0, 129.4, 125.8 and 125.6, 123.4 and 123.2, 116.5 and 116.2, 114.3 and 114.1, 112.3, 108.9, 53.3 and 52.8. ESI-HRMS(m/z):Calcd. for C 16 H 14 N 3 O 3 [M+H] + 296.1035; found 296.1030。
Example 18
(4-oxo-4H-quinolin-1-yl) -acetyl (thiophen-2-ylmethylene) hydrazine (I) 18 ) The aldehyde is thiophene-2-formaldehyde.
0.2781g of white solid was found to be 89.4% yield. Melting point 290 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.87 and 11.81 (s, 1H), 8.47 and 8.27 (s, 1H), 8.18 (d, J = 8.0 Hz, 1H), 8.00 - 7.98 (d, J = 7.6 Hz, 1H), 7.73 - 7.65 (m, 2H), 7.51 - 7.49 (m, 1H), 7.47 - 7.34 (m, 2H), 7.16 - 7.13 (m, 1H), 6.11 - 6.08 (m, 1H), 5.42 and 5.05 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.6, 167.8 and 163.1, 145.7 and 145.6, 142.9 and 139.6, 140.6 and 140.4, 138.6 and 138.5, 132.1 and 132.0, 131.4 and 130.9, 129.2 and 128.9, 127.9, 126.4, 125.7 and 125.5, 123.3 and 123.2, 116.4 and 116.1, 108.8, 53.2 and 52.6. ESI-HRMS(m/z):Calcd. for C 16 H 14 N 3 O 2 S[M+H] + 312.0807; found 312.0802。
Example 19
(4-oxo-4H-quinolin-1-yl) -acetyl (thiazol-4-ylmethylene) hydrazine (I) 19 ) The aldehyde is thiazole-4-formaldehyde.
0.1695g of white solid was found to be 54.3% yield. Melting point 226 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.95 and 11.89 (s, 1H), 9.21 -9.18 (m, 1H), 8.41 and 8.26 - 8.16 (m, 3H), 8.01 - 7.97 (m, 1H), 7.73 - 7.65 (m, 1H), 7.49 - 7.35 (m, 2H), 6.11 - 6.08 (m, 1H), 5.49 and 5.08 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.6, 168.2 and 163.4, 155.2 and 155.1, 151.2 and 151.1, 145.7 and 145.6, 140.6 and 140.4, 139.1, 132.1 and 132.0, 126.4, 125.7 and 125.6, 123.3 and 123.2, 120.2 and 119.9, 116.4 and 115.6, 108.8, 53.3 and 52.7. ESI-HRMS(m/z):Calcd. for C 15 H 13 N 4 O 2 S[M+H] + 313.0759; found 313.0753。
Example 20
(4-oxo-4H-quinolin-1-yl) -acetyl (indol-2-ylmethylene) hydrazine (I) 20 ) The aldehyde is indole-2-carbaldehyde.
Yellow solid 0.1505g, 43.8% yield. The melting point is greater than 300 ℃. 1 H NMR (400 Hz, DMSO-d 6 ) 11.89 (s, 1H), 11.56 - 11.48 (s, 1H), 8.30 and 8.11 (s, 1H), 8.22 - 8.19 (m, 1H), 8.05 and 8.00 (d, J = 7.6 Hz, 1H), 7.74 - 7.69 (m, 1H), 7.59 - 7.37 (m, 4H), 7.21 - 7.13 (m, 1H), 7.05 - 7.00 (m, 1H), 6.87 (s, 1H), 6.12 (d, J = 8.0 Hz, 1H), 5.61 and 5.09 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.6, 168.2 and 163.6, 145.8 and 145.6, 140.5, 137.9 and 137.5, 136.6, 133.2 and 132.7, 132.1, 127.8 and 127.5, 126.5, 125.7, 123.5 and 123.4, 123.3 and 123.2, 121.0 and 120.8, 119.6, 116.2, 112.0 and 111.5, 108.9, 107.4 and 106.4, 53.4 and 52.6. ESI-HRMS(m/z):Calcd. for C 20 H 17 N 4 O 2 [M+H] + 345.1352; found 345.1347。
Example 21
(4-oxo-4H-quinolin-1-yl) -acetyl (benzofuran-3-ylmethylene) hydrazine (I 21 ) The aldehyde is benzofuran-3-carbaldehyde.
White solid 0.3296g, yield 95.5%. Melting point 260 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.97 and 11.89 (s, 1H), 8.55 (m, 1H), 8.47 and 8.31 (s, 1H), 8.32 (d, J = 8.0 Hz, 1H), 8.22 - 8.18 (m, 1H), 8.06 - 7.99 (m, 1H), 7.72 and 7.63 (m, 2H), 7.54 - 7.35 (m, 4H), 6.12 (d, J = 8.0 Hz, 1H), 5.63 and 5.10 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.0 and 162.9, 155.2 and 154.3, 149.5 and 149.3, 145.8 and 145.7, 141.0 and 140.8, 138.1, 132.2 and 132.0, 126.5 and 126.4, 125.7, 125.6, 124.0, 123.8 and 123.7, 123.4 and 123.2, 117.5 and 117.4, 116.7 and 116.2, 111.5, 108.9, 53.3 and 52.9. ESI-HRMS(m/z):Calcd. for C 20 H 16 N 3 O 3 [M+H] + 346.1192; found 346.1187。
Example 22
(4-oxo-4H-quinolin-1-yl) -acetyl (9-ethyl-9H-carbazol-3-ylmethylene) hydrazine (I) 22 ) The aldehyde is 9-ethyl-9H-carbazole-3-carbaldehyde.
0.3214g of white solid was found to be 78.8% yield. The melting point is greater than 300 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.84 and 11.78 (s, 1H), 8.55 and 8.46 (s, 1H), 8.25 - 8.19 (m, 3H), 8.06 - 7.95 (m, 2H), 7.74 - 7.64 (m, 3H), 7.54 - 7.48 (m, 2H), 7.41 - 7.36 (m, 1H), 7.27 - 7.23 (m, 1H), 6.13 - 6.10 (m, 1H), 5.61 and 5.08 (s, 2H), 4.49 (q, J = 6.80 Hz, 2H), 1.34 (t, J = 6.80 Hz, 3H). 13 C NMR (100Hz, DMSO-d 6 ) 176.6, 167.9, 145.8 and 145.6, 145.5, 140.7, 140.6, 140.0, 132.1 and 132.0, 126.4, 126.2, 125.7 and 125.6, 124.9, 124.5, 123.2, 122.3, 122.1, 120.6, 120.3, 119.3, 116.5 and 116.0, 109.5, 109.4, 108.8, 52.9, 37.1, 13.7. ESI-HRMS(m/z):Calcd. for C 26 H 23 N 4 O 2 [M+H] + 423.1821; found 423.1814。
Example 23
(4-oxo-4H-quinolin-1-yl) -acetyl (3, 4-dimethoxybenzylidene) hydrazine (I) 23 ) The aldehyde is 3, 4-dimethoxy benzaldehyde.
0.2902g of yellow solid with a yield of 79.5% and a melting point of 170 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.79 and 11.74 (s, 1H), 8.20 - 8.17 (m, 1H), 8.02 -7.97 (m, 2H), 7.70 - 7.66 (m, 1H), 7.49 - 7.35 (m, 3H), 7.29 - 7.24 (m, 1H), 7.04 - 7.01 (m, 1H), 6.11 - 6.08 (m, 1H), 5.54 and 5.05 (s, 2H), 3.82 - 3.78 (m, 6H). 13 C NMR (100Hz, DMSO-d 6 ) 176.5, 168.0 and 162.8, 150.7, 149.0, 145.7 and 145.6, 144.4, 140.7, 132.1 and 131.9, 126.6 and 126.5, 126.4, 125.5, 123.3 and 123.1, 121.9 and 121.6, 116.5, 111.5, 108.8, 108.7, 55.6, 55.5, 52.9. ESI-HRMS(m/z):Calcd. for C 20 H 20 N 3 O 4 [M+H] + 366.1454; found 366.1446。
Example 24
(4-oxo-4H-quinolin-1-yl) -acetyl (5-bromo-2-methoxybenzylidene) hydrazine (I 24 ) The aldehyde is 5-bromo-2-methoxybenzaldehyde.
Yellow solid 0.3296g, yield 79.6%. Melting point 290 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.04 and 11.87 (s, 1H), 8.34 (s, 1H), 8.19 (d, J = 7.6 Hz, 1H), 8.10 (s, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.69 - 7.65 (m, 1H), 7.58 (d, J = 9.2 Hz, 1H), 7.46 (d. J = 8.8 Hz, 1H), 7.38 - 7.34 (m, 1H), 7.10 (d, J = 8.8 Hz, 1H), 6.09 (d, J = 7.6 Hz, 1H), 5.58 and 5.06 (s, 2H), 3.87 (s, 3H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.4, 156.9, 145.8 and 145.6, 140.7 and 140.5, 138.4, 133.9 and 133.8, 132.2 and 131.9, 127.7 and 127.5, 126.5 and 126.4, 125.8 and 125.5, 124.1 and 124.0, 123.4 and 123.2, 116.7 and 116.2, 114.5 and 114.3, 112.7 and 112.5, 108.9 and 108.8, 56.2, 53.4 and 53.0. ESI-HRMS(m/z):Calcd. for C 19 H 17 BrN 3 O 3 [M+H] + 414.0453; found 414.0452。
Example 25
(4-oxo-4H-quinolin-1-yl) -acetyl (3, 5-dibromo-4-hydroxybenzylidene) hydrazine (I 25 ) The aldehyde is 3, 5-dibromo-4-hydroxybenzaldehyde.
0.433g of pale yellow solid is obtained with a yield of 90.4%. Melting point 295 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.00 and 11.86 (s, 1H), 8.18 (d, J = 8.0 Hz, 1H), 8.01 -7.80 (m, 4H), 7.71 - 7.65 (m, 1H), 7.48 -7.44 (m, 1H), 7.38 - 7.34 (m, 1H), 6.11 - 6.08 (m, 1H), 5.57 and 5.06 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.4, 152.2, 145.6, 141.6, 140.7 and 140.5, 132.0, 130.8, 128.5, 126.4, 125.5, 123.2, 116.8, 112.2 and 112.1, 108.8, 53.0. ESI-HRMS(m/z):Calcd. for C 18 H 14 Br 2 N 3 O 3 [M+H] + 477.9402; found 477.9401。
Example 26
The tobacco mosaic virus resistance activity was measured as follows:
1. virus purification and concentration determination:
the virus purification and concentration measurement are carried out by compiling tobacco mosaic virus SOP standard according to a measuring room generated by elements of university of south China. After 2 times of polyethylene glycol centrifugation treatment, the concentration of the virus crude extract is measured, and the virus crude extract is refrigerated at 4 ℃ for standby.
2. Compound solution preparation:
after weighing, adding DMF to dissolve the raw materials to obtain 1×10 5 Mu g/mL mother liquor, and then diluting the mother liquor to the required concentration by using an aqueous solution containing 1 permillage Tween 80; the Ningnan mycin preparation is directly diluted by water.
3. In vivo passivation:
selecting 3-5 She Qishan Xie smoke with uniform growth vigor, mixing the medicament with an equal volume of virus juice, inactivating for 30 min, performing friction inoculation, wherein the virus concentration is 20 mu g/mL, washing with running water after inoculation, repeating for 3 times, and setting 1 millTween 80 aqueous solution for comparison. The number of lesions was counted after 3 d and the result was calculated.
4. In vivo therapeutic action:
3-5 She Qishan Xiyan with uniform growth vigor is selected, virus is inoculated to whole leaves of a writing brush, the virus concentration is 10 mu g/mL, and the whole leaves are washed by flowing water after inoculation. After leaf surface is dried, spraying and applying the whole plant, repeating for 3 times every treatment, and setting 1%Tween 80 water solution as a control. And 3, after d, recording the number of the lesions, and calculating the control effect.
5. Living body protecting action:
3-5 She Qishan Xiyan with uniform growth vigor is selected, the whole plant is sprayed and applied, each treatment is repeated for 3 times, and 1 permillage of Tween 80 aqueous solution is used for comparison. 24 After h, the leaf surface is spread with silicon carbide (500 meshes), the whole leaf surface is dipped with a virus liquid by a writing brush, the whole leaf surface is lightly rubbed for 2 times along the branch pulse direction, the lower part of the leaf surface is supported by a palm, the virus concentration is 10 mu g/mL, and the leaf surface is washed by running water after inoculation. And 3, after d, recording the number of the lesions, and calculating the control effect.
Inhibition ratio (%) = [ (control number of dried spots-number of treated dried spots)/control number of dried spots ] ×100%.
Tables 1 to 8 show quinolinone alkaloid derivatives I 1 -I 25 Is of the structure of (a)
TABLE 1
TABLE 2
TABLE 3 Table 3
TABLE 4 Table 4
TABLE 5
TABLE 6
TABLE 7
TABLE 8
Tables 9-12 are quinolinone alkaloid derivatives I 1 -I 25 Is effective in resisting tobacco mosaic virus
TABLE 9
Table 10
TABLE 11
Table 12
Claims (8)
1. A quinolinone alkaloid derivative containing an acylhydrazone group on the nitrogen atom at position 1, characterized in that: the structural general formula is as followsThe formula (I) is as follows:
wherein R is selected from naphthyl or substituted phenyl;
the substituent in the substituted phenyl is selected from any one or 2-3 substituents in hydrogen, hydroxyl, halogen atom, cyano, nitro, trifluoromethyl, trifluoromethoxy, 1-5 carbon alkyl and 1-6 carbon alkoxy.
2. A quinolinone alkaloid derivative containing an acylhydrazone group on the nitrogen atom at position 1, characterized by a structure selected from the group consisting of:
wherein R is phenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-biphenyl, 3-methoxyphenyl, 4-methylthiophenyl, 4-methylsulfonylphenyl, 4- (pyrazol-1-yl) phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-nitrophenyl, 4-trifluoromethylphenyl, 4-dimethylaminophenyl, 2-nitrophenyl, pyridin-3-yl, furan-2-yl, thiophen-2-yl, thiazol-4-yl, indol-2-yl, benzofuran-3-yl, 9-ethyl-9H-carbazol-3-yl, 3, 4-dimethoxyphenyl, 5-bromo-2-methoxyphenyl, (4-oxo-3, 5-dibromo-4-hydroxyphenyl).
3. A process for the preparation of quinolinone alkaloid derivatives containing an acylhydrazone group on the nitrogen atom in position 1 as defined in claim 1 or 2, characterized in that: the method comprises the following steps:
firstly, reacting 1H-quinolin-4-one with alpha-bromoethyl acetate in a solvent in the presence of a base at room temperature to form (oxo-4H-quinolin-1-yl) -ethyl acetate;
secondly, reacting (oxo-4H-quinolin-1-yl) -ethyl acetate with water and hydrazine in a solvent to form (4-oxo-4H-quinolin-1-yl) -acethydrazide;
thirdly, reacting (4-oxo-4H-quinolin-1-yl) -acethydrazide with aldehyde in a solvent to form a quinolinone alkaloid derivative having an acylhydrazone group on the 1-position nitrogen atom.
4. A process for the preparation of quinolinone alkaloid derivatives containing an acylhydrazone group on the nitrogen atom in position 1 according to claim 3, characterized in that: the solvent in the first step is selected from N, N-dimethylformamide; the base is selected from any one of cesium carbonate, sodium carbonate and potassium carbonate.
5. A process for the preparation of quinolinone alkaloid derivatives containing an acylhydrazone group on the nitrogen atom in position 1 according to claim 3, characterized in that: in the second step the solvent is selected from methanol; the reaction temperature was 65 ℃.
6. A process for the preparation of quinolinone alkaloid derivatives containing an acylhydrazone group on the nitrogen atom in position 1 according to claim 3, characterized in that: the solvent in the third step is selected from any one of methanol, ethanol and acetonitrile; the temperature of the reaction is 20-130 ℃.
7. A process for the preparation of quinolinone alkaloid derivatives containing an acylhydrazone group on the nitrogen atom in position 1 according to claim 3, characterized in that: in the third step, the aldehyde is selected from any one of benzaldehyde, 4-methylbenzaldehyde, 4-tert-butylbenzaldehyde, 4-phenylbenzaldehyde, 3-methoxybenzaldehyde, 4-methylthiobenzaldehyde, 4-methylsulfonylbenzaldehyde, pyrazol-1-ylbenzaldehyde, 4-fluorobenzaldehyde, 4-chlorobenzaldehyde, 4-bromobenzaldehyde, 4-nitrobenzaldehyde, 4-trifluoromethylbenzaldehyde, 4-dimethylaminobenzaldehyde, 2-nitrobenzaldehyde, pyridine-3-formaldehyde, furan-2-formaldehyde, thiophene-2-formaldehyde, thiazole-4-formaldehyde, indole-2-formaldehyde, benzofuran-3-formaldehyde, 9-ethyl-9H-carbazole-3-formaldehyde, 3, 4-dimethoxybenzaldehyde, 5-bromo-2-methoxybenzaldehyde and 3, 5-dibromo-4-hydroxybenzaldehyde.
8. Use of a quinolinone alkaloid derivative containing an acylhydrazone group on the 1-position nitrogen atom as defined in claim 1 or 2 for controlling tobacco mosaic virus.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210783046.XA CN115232070B (en) | 2022-07-05 | 2022-07-05 | Quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210783046.XA CN115232070B (en) | 2022-07-05 | 2022-07-05 | Quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115232070A CN115232070A (en) | 2022-10-25 |
| CN115232070B true CN115232070B (en) | 2023-06-30 |
Family
ID=83670718
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210783046.XA Active CN115232070B (en) | 2022-07-05 | 2022-07-05 | Quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115232070B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019071911A1 (en) * | 2017-10-13 | 2019-04-18 | 南开大学 | 5a5b6c tricyclic spirolactone derivative, preparation method therefor and use thereof |
| US10709166B2 (en) * | 2012-07-19 | 2020-07-14 | R.J. Reynolds Tobacco Company | Method for treating tobacco plants with enzymes |
| CN112624969A (en) * | 2019-09-24 | 2021-04-09 | 南开大学 | Quinoline derivative, preparation method thereof and application thereof in preventing and treating plant viruses and killing bacteria |
| CN113735769A (en) * | 2021-09-26 | 2021-12-03 | 太原理工大学 | Quinolinone alkaloid derivative containing acylhydrazone structure at 3-position and preparation method and application thereof |
-
2022
- 2022-07-05 CN CN202210783046.XA patent/CN115232070B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10709166B2 (en) * | 2012-07-19 | 2020-07-14 | R.J. Reynolds Tobacco Company | Method for treating tobacco plants with enzymes |
| WO2019071911A1 (en) * | 2017-10-13 | 2019-04-18 | 南开大学 | 5a5b6c tricyclic spirolactone derivative, preparation method therefor and use thereof |
| CN112624969A (en) * | 2019-09-24 | 2021-04-09 | 南开大学 | Quinoline derivative, preparation method thereof and application thereof in preventing and treating plant viruses and killing bacteria |
| CN113735769A (en) * | 2021-09-26 | 2021-12-03 | 太原理工大学 | Quinolinone alkaloid derivative containing acylhydrazone structure at 3-position and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| "TWO NEW ANTI-TOBACCO MOSAIC VIRUS QUINOLIN-2(1H)-ONES FROM THE TWIGS OF Cassia auriculata";Chao-Pei Zheng et al.;《Chemistry of Natural Compounds》;第59卷;第107-110页 * |
| "金丝马尾连中1个具有抗病毒活性的异喹啉新生物碱";罗甸等;《中国中药杂志》;第2568-2570页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115232070A (en) | 2022-10-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Xiangming et al. | p-TsOH catalyzed synthesis of 2-arylsubstituted benzimidazoles | |
| CZ291040B6 (en) | Trisubstituted phenyl derivatives and pharmaceutical composition containing them | |
| Stojiljković et al. | The reaction of lead tetraacetate with primary and secondary amines containing an α-methylene group | |
| CN115232070B (en) | Quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom, and preparation method and application thereof | |
| WO2007006591A2 (en) | Dihalogenation of n,o-disubstituted hydroxipyridones and uses thereof | |
| Nasr-Esfahani et al. | An efficient Hantzsch synthesis of 1, 4-dihydropyridines using p-toluenesulfonic acid under solvent-free condition | |
| CN112250636A (en) | 5-aminoimidazole compound and synthesis method thereof | |
| Kashima et al. | Preparation of 2, 6‐bis (l‐menthopyrzol‐3‐yl) pyridines and their catalytic activity for asymmetric diels alder reaction | |
| CN112209894B (en) | 5-aryl substituted 2-aminobenzoxazole derivative, preparation method and application thereof | |
| Pinder et al. | 2-Aminoindan-2-carboxylic acids. Potential tyrosine hydroxylase inhibitors | |
| SU602112A3 (en) | Method of producing amines, their salts, racemates or optically-active antipodes | |
| EP3282845A1 (en) | (s)-2'-vinyl-abscisic acid derivatives | |
| Heravi et al. | KHSO4 Supported Onto Bentonite, A Versatile Reagent for Aromatization of Hantzsch 1, 4‐Dihydropyridines | |
| FR2576020A1 (en) | 5-HALOPYRIDINE-3-CARBOXAMIDES AND THEIR APPLICATIONS | |
| US6005118A (en) | Methods of preparing 4-cyano-4 (substituted indazole) cyclohexane-carboxylic acids useful as PDE4 inhibitors | |
| EP0095104A2 (en) | Process for the preparation of pyridyl and quinolyl imidazolinones | |
| RU2001128428A (en) | Synthesis of 3-amino-3-arylpropanoates | |
| KR100578425B1 (en) | Cathecol Hydrazine Derivatives, Process for Producing the Same and Pharmaceutical Composition Containing the Same | |
| CN113943309B (en) | Indolospiro [ benzofuran-2, 2' -pyrrolidine ] compound, preparation method thereof and application thereof in preventing and treating plant viruses | |
| CN116283821B (en) | Phencyclized propylamine compound, preparation method and application | |
| CN114380815B (en) | Plant protection camalexin derivative and preparation method and application thereof | |
| US5889018A (en) | Heterocyclic compounds, pharmaceutical compositions comprising them and process for the preparation thereof | |
| KR101580821B1 (en) | Development of a New Synthetic Method for Quinazolinones via Aerobic Oxidation in dimethylsulfoxide | |
| Xu et al. | Enantioselective synthesis of new dimeric chromene derivatives by a ferrocene-copper catalyst system | |
| Rezayati et al. | Phospho sulfonic acid: an efficient solid acid catalyst for the facile preparation of 1, 4-dihydropyridines |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |