CN116003319A - Sulfur-containing quinoline compound and preparation method and application thereof - Google Patents
Sulfur-containing quinoline compound and preparation method and application thereof Download PDFInfo
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- CN116003319A CN116003319A CN202211532975.XA CN202211532975A CN116003319A CN 116003319 A CN116003319 A CN 116003319A CN 202211532975 A CN202211532975 A CN 202211532975A CN 116003319 A CN116003319 A CN 116003319A
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 title claims abstract description 18
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 229910052717 sulfur Inorganic materials 0.000 title claims abstract description 18
- 239000011593 sulfur Substances 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- -1 quinoline compound Chemical class 0.000 title claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 44
- 125000001424 substituent group Chemical group 0.000 claims abstract description 21
- 125000003435 aroyl group Chemical group 0.000 claims abstract description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 6
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract 4
- 150000002367 halogens Chemical class 0.000 claims abstract 4
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 150000003248 quinolines Chemical class 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 claims description 5
- FNENWZWNOPCZGK-UHFFFAOYSA-N ethyl 2-methyl-3-oxobutanoate Chemical compound CCOC(=O)C(C)C(C)=O FNENWZWNOPCZGK-UHFFFAOYSA-N 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 230000000855 fungicidal effect Effects 0.000 claims 1
- 239000000417 fungicide Substances 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 13
- 239000003899 bactericide agent Substances 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000001035 drying Methods 0.000 description 7
- 230000001580 bacterial effect Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 240000008067 Cucumis sativus Species 0.000 description 3
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000233616 Phytophthora capsici Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241000123650 Botrytis cinerea Species 0.000 description 2
- 235000002566 Capsicum Nutrition 0.000 description 2
- 241000223218 Fusarium Species 0.000 description 2
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 2
- 239000006002 Pepper Substances 0.000 description 2
- 235000016761 Piper aduncum Nutrition 0.000 description 2
- 235000017804 Piper guineense Nutrition 0.000 description 2
- 244000203593 Piper nigrum Species 0.000 description 2
- 235000008184 Piper nigrum Nutrition 0.000 description 2
- 206010039509 Scab Diseases 0.000 description 2
- 241000221696 Sclerotinia sclerotiorum Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 240000003768 Solanum lycopersicum Species 0.000 description 2
- 241000209140 Triticum Species 0.000 description 2
- 235000021307 Triticum Nutrition 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 241000213004 Alternaria solani Species 0.000 description 1
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- 241000190146 Botryosphaeria Species 0.000 description 1
- 241000223195 Fusarium graminearum Species 0.000 description 1
- 241000223221 Fusarium oxysporum Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241000315044 Passalora arachidicola Species 0.000 description 1
- 241000231139 Pyricularia Species 0.000 description 1
- 241000813090 Rhizoctonia solani Species 0.000 description 1
- 241001558929 Sclerotium <basidiomycota> Species 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 230000002365 anti-tubercular Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000010413 mother solution Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
Classifications
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- 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
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a sulfur-containing quinoline compound, a preparation method and application thereof, wherein the structural formula of the sulfur-containing quinoline compound is shown as the formula (I):
wherein H on the benzene ring is not substituted by R 1 R is R when substituted 2 Is alkyl, acetonitrile, propenyl, alkyl ester methylene, benzyl, substituted benzyl or alkoxycarbonyl, and the substituent for substituted benzyl is halogen or alkyl; h on the benzene ring being substituted, substituent R 1 In the case of tert-butyl, R 2 Is aroyl or substituted aroyl, the substituent of the substituted aroyl is alkylAn alkoxy group or a halogen. The sulfur-containing quinoline compound provided by the invention is a novel compound with good bactericidal activity, and provides a basis for researching natural green bactericides.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis and pharmaceutical application, and particularly relates to a sulfur-containing quinoline compound, and a preparation method and application thereof.
Background
Quinoline derivatives are an important class of heterocyclic aromatic compounds. In modern synthetic chemistry, quinoline compounds are widely used in a variety of fields such as coordination chemistry, organometallic chemistry, asymmetric synthesis, pharmaceutical chemistry, agrochemical chemistry, and material chemistry. The excellent antitubercular, antimalarial, bactericidal and insecticidal activities of quinoline compounds attract a plurality of scientists.
Quinoline is a structure with strong medicinal physiological activity, and the structure is easy to modify. The introduction of different drug molecules into the quinoline structure will alter or enhance its activity, which provides the basis for the synthesis of lead compounds, modification and modification of the drug structure. In conclusion, the research on quinoline compounds is long-standing.
Disclosure of Invention
The invention aims to provide a quinoline compound containing sulfur, and a preparation method and application thereof.
The invention provides a sulfur-containing quinoline compound, which has a structural formula shown in a formula (I):
wherein H on the benzene ring is not substituted by R 1 R is R when substituted 2 Is alkyl, acetonitrile, propenyl, alkyl ester methylene, benzyl, substituted benzyl or alkoxycarbonyl;
h on the benzene ring being substituted, R 1 In the case of tert-butyl, R 2 Is aroyl or substituted aroyl.
Preferably, the substituent for the substituted benzyl group is 2-chloro, 4-fluoro, 4-t-butyl, 4-bromo, 4-methyl, 2, 4-dichloro, 3, 4-dichloro, 2-fluoro, 3-fluoro or 4-chloro; the substituent of the substituted aroyl group is 4-tert-butyl, 2-methyl, 3-methyl, 4-methyl, 2-fluoro, 3-fluoro, 4-fluoro, 3-chloro, 4-chloro, 2, 3-dichloro, 3, 4-dichloro, 4-n-propyl, 2-methoxy or 4-methoxy.
The invention also provides a preparation method of the quinoline compound containing sulfur, which comprises the following steps of;
1) Reacting a compound shown as a formula (II) with ethyl 2-methyl acetoacetate by taking polyphosphoric acid as a cyclizing agent to generate a compound shown as a formula (III);
2) Reacting the compound shown in the formula (III) obtained in the step 1) with a Lawsen reagent by using THF as a solvent to obtain a compound shown in the formula (IV);
3) Providing an alkaline environment by using DCM or DMF as a solvent and triethylamine or sodium hydroxide, and reacting the compound shown in the formula (IV) obtained in the step 2) with a compound shown in the formula (V) to obtain quinoline compounds containing a thioester bond shown in the formula (I);
wherein H on the benzene ring is not substituted by R 1 R is R when substituted 2 Is alkyl, acetonitrile, propenyl, alkyl ester methylene, benzyl, substituted benzyl or alkoxycarbonyl, the substituent of the substituted benzyl is 2-chloro, 4-fluoro, 4-tert-butyl, 4-bromo, 4-methyl, 2, 4-dichloro, 3, 4-dichloro, 2-fluoro, 3-fluoro or 4-chloro;
when H on the benzene ring is substituted, R 1 In the case of tert-butyl, R 2 For aroyl or substituted aroyl, the substituent of substituted aroyl is 4-tert-butyl, 2-methyl, 3-methyl, 4-methyl, 2-fluoro, 3-fluoro, 4-fluoro, 3-chloro, 4-chloro, 2, 3-dichloro, 3, 4-dichloro, 4-n-propyl, 2-methoxy or 4-methoxy.
The reaction process is as follows:
wherein H on the benzene ring is not substituted by R 1 R is R when substituted 2 Is alkyl, acetonitrile, propenyl, alkyl ester methylene, benzyl, substituted benzyl or alkoxycarbonyl, the substituent of the substituted benzyl is 2-chloro, 4-fluoro, 4-tert-butyl, 4-bromo, 4-methyl, 24-dichloro, 3, 4-dichloro, 2-fluoro, 3-fluoro or 4-chloro;
h on the benzene ring being substituted, R 1 In the case of tert-butyl, R 2 For aroyl or substituted aroyl, the substituent of substituted aroyl is 4-tert-butyl, 2-methyl, 3-methyl, 4-methyl, 2-fluoro, 3-fluoro, 4-fluoro, 3-chloro, 4-chloro, 2, 3-dichloro, 3, 4-dichloro, 4-n-propyl, 2-methoxy or 4-methoxy.
Further, when the compound shown in the formula (III) is synthesized in the step 1), the mass ratio of the compound shown in the formula (II) to the substance of the 2-methyl acetoacetic acid ethyl ester is 1:1-1:1.5.
Further, when the compound shown in the formula (IV) is synthesized in the step 2), the mass ratio of the compound shown in the formula (III) to the substance of the Lawson reagent is 1:0.5-1:1.
Further, the mass ratio of the compound shown in the formula (IV) to the compound shown in the formula (V) is 1:1-1:1.5.
The invention also provides application of the sulfur-containing quinoline compound in preparation of bactericides.
The invention has the beneficial effects that:
the preparation method has simple process and no need of additional metal catalysis, and the structure of the obtained product is improved 1 H NMR and HRMS prove that the product has a certain bactericidal effect on different germs.
Detailed Description
The invention will be further illustrated with reference to specific examples, but the scope of the invention is not limited thereto.
The reaction equation is as follows:
examples 1-2 preparation of Compounds III-1 to III-2
Into a 250mL three-necked flask, 100.00mmol of a compound represented by formula (II) (wherein H on the benzene ring is substituted by R 1 Substituted or unsubstituted, R being the substituent 1 Is tert-butyl)Ethyl 2-methylacetoacetate (14.42 g,100.00 mmol), polyphosphoric acid (50.69 g,150.00 mmol), and TLC (V) EA /V PE =1/1) tracking the reaction progress, stopping the reaction after 5 hours, cooling to room temperature, putting the reaction bottle into an ice bath, adjusting the pH to 7 by using a sodium hydroxide aqueous solution with the mass concentration of 10%, precipitating a large amount of solids, carrying out suction filtration, taking a filter cake, and drying to obtain the compounds III-1 to III-2.
Examples 3-4 preparation of Compounds IV-1 to IV-2
Into a 100mL three-necked flask, 30.00mmol of a compound represented by the formula (III) wherein H on the benzene ring is substituted with the substituent R 1 Substituted or unsubstituted, R being the substituent 1 Tert-butyl) and Lawson's reagent (8.09 g,20.00 mmol), and THF (30 mL) was added, heated to reflux, TLC (V) EA /V PE =1/1) the progress of the reaction was followed, after the end of the reaction, the solvent was dried by spinning, the residue was dissolved in ethyl acetate solution and transferred to a separatory funnel, and saturated NaHCO was used 3 Washing the solution (20 mL multiplied by 3), drying by anhydrous sodium sulfate, filtering, spin-drying the solvent, and purifying by column chromatography to obtain the compounds IV-1 to IV-2.
EXAMPLES 5-20 preparation of Compounds I-1 to I-16
A50 mL round-bottomed flask was charged with the compound represented by the formula (IV) (0.20 g,0.96 mmol), sodium hydroxide (0.05 g,1.25 mmol) and DMF (5 mL) in this order, and after stirring at room temperature for half an hour, 1.01mmol of the compound represented by the formula (V) (corresponding substituent R) 1 And R is 2 Stirring was continued as shown in Table 1, TLC (V) EA /V PE =1/4), after the reaction, transferring to a separating funnel, adding water (15 mL), extracting with ethyl acetate (5 ml×3), mixing the organic phases, washing with saturated saline (5 ml×3), drying with anhydrous sodium sulfate, filtering, spin-drying the solvent, and purifying by column chromatography to obtain the target compounds I-1 to I-16.
Examples 21-39 preparation of Compounds I-17 to I-35
A50 mL round-bottomed flask was charged with the compound represented by the formula (IV) (0.96 mmol), triethylamine (0.5 mmol) and DCM (5 mL) in this order, and after stirring at room temperature for half an hour, the compound represented by the formula (V) was added(1.06 mmol) (corresponding substituent R 1 And R is 2 Stirring was continued as shown in Table 1, TLC (V) EA /V PE =1/4), after the reaction, transferring to a separating funnel, adding water (15 mL), extracting with ethyl acetate (5 ml×3), mixing the organic phases, washing with saturated saline (5 ml×3), drying with anhydrous sodium sulfate, filtering, spin-drying the solvent, and purifying by column chromatography to obtain the target compounds I-17 to I-35.
TABLE 1 physical Properties of quinoline Compounds containing Sulfur
TABLE 2 characterization data for quinoline Compounds containing Sulfur
EXAMPLE 40 bactericidal Activity test
Test method
(1) Test object: tomato early blight (Alternaria solani), wheat scab (Gibberella zeae), rice blast (Pyricularia oryae), pepper phytophthora capsici (Phytophthora capsici), sclerotinia sclerotiorum (Sclerotinia sclerotiorum), cucumber Botrytis cinerea (Botrytis cinerea), rhizoctonia solani (Riziocotinia solani), cucumber fusarium wilt (Fusarium oxysporum), peanut brown spot (Cercospora arachidicola) and apple ring rot (Botryosphaeria berengriana)
(2) Test treatment: each test compound was dissolved in DMSO to 1% EC mother liquor for use. The indoor bactericidal activity of the compound to be tested on the test target at the dose of 50ppm is evaluated by adopting a bacteriostasis circle method, and a water control (QCK) is additionally arranged.
(3) The test method comprises the following steps: 150. Mu.l of the EC mother solution thus prepared was sucked by a pipette and dissolved in 2.85mL of warm water to prepare a drug solution having an effective concentration of 500ppm of the compound to be tested. 1ml of the liquid medicine is sucked by a pipette, placed in a sterilized culture dish, placed in 9ml of PDA culture medium, shaken uniformly and cooled. After taking out the circular bacterial cake by a puncher, picking up the circular bacterial cake to the center of a culture dish by an inoculating needle, then placing the culture dish in an incubator at 27 ℃ for culturing, and measuring the colony diameter after 48 hours. The pure growth of the bacterial colony is the difference value between the average diameter of the bacterial colony and the diameter of a bacterial cake, and the calculation method of the bacteriostasis rate (%) refers to the following formula.
The activity test results are shown in table 3:
TABLE 3 bactericidal activity of quinoline containing sulfur
The results of the bactericidal activity of 35 quinoline compounds containing sulfur show that (table 3) under the concentration of 50ppm, the compound I-12 has good bactericidal activity, the bactericidal activity for wheat scab is 75.0%, and the bactericidal activity for two germs of sclerotium and apple ring rot are 88.5% and 81.2%, respectively. In addition, the bactericidal activity of the compound I-12 on tomato early blight bacteria, pepper phytophthora capsici and cucumber fusarium wilt bacteria respectively reaches 56.3%, 58.1% and 55.0%.
What has been described in this specification is merely an enumeration of possible forms of implementation for the inventive concept, and the scope of protection of the present invention should not be construed as limited to the specific forms set forth in the examples, nor is it intended that the scope of protection of the present invention be limited to only equivalent technical means as would occur to those skilled in the art based on the inventive concept.
Claims (7)
1. A sulfur-containing quinoline compound is characterized in that the structural formula is shown as a formula (I):
wherein H on the benzene ring is not substituted by R 1 R is R when substituted 2 Is alkyl, acetonitrile, propenyl, alkyl ester methylene, benzyl, substituted benzyl or alkoxycarbonyl, and the substituent for substituted benzyl is halogen or alkyl;
h on the benzene ring being substituted, substituent R 1 In the case of tert-butyl, R 2 Is aroyl or substituted aroyl, and the substituent of the substituted aroyl is alkyl, alkoxy or halogen.
2. A sulfur-containing quinoline compound according to claim 1 wherein the substituent substituted for the benzyl group is 2-chloro, 4-fluoro, 4-t-butyl, 4-bromo, 4-methyl, 2, 4-dichloro, 3, 4-dichloro, 2-fluoro, 3-fluoro or 4-chloro; the substituent of the substituted aroyl group is 4-tert-butyl, 2-methyl, 3-methyl, 4-methyl, 2-fluoro, 3-fluoro, 4-fluoro, 3-chloro, 4-chloro, 2, 3-dichloro, 3, 4-dichloro, 4-n-propyl, 2-methoxy or 4-methoxy.
3. A process for the preparation of a sulfur-containing quinoline compound according to claim 2, comprising the steps of:
1) Reacting a compound shown as a formula (II) with ethyl 2-methyl acetoacetate by taking polyphosphoric acid as a cyclizing agent to generate a compound shown as a formula (III);
2) Reacting the compound shown in the formula (III) obtained in the step 1) with a Lawsen reagent by using THF as a solvent to obtain a compound shown in the formula (IV);
3) Providing an alkaline environment by using DCM or DMF as a solvent and triethylamine or sodium hydroxide, and reacting the compound shown in the formula (IV) obtained in the step 2) with a compound shown in the formula (V) to obtain quinoline compounds containing a thioester bond shown in the formula (I);
wherein H on the benzene ring is not substituted by R 1 R is R when substituted 2 Is alkyl, acetonitrile, propenyl, alkyl ester methylene, benzyl, substituted benzyl or alkoxycarbonyl, the substituent of the substituted benzyl is 2-chloro, 4-fluoro, 4-tert-butyl, 4-bromo, 4-methyl, 2, 4-dichloro, 3, 4-dichloro, 2-fluoro, 3-fluoro or 4-chloro;
when H on the benzene ring is substituted, R 1 In the case of tert-butyl, R 2 For aroyl or substituted aroyl, the substituent of substituted aroyl is 4-tert-butyl, 2-methyl, 3-methyl, 4-methyl, 2-fluoro, 3-fluoro, 4-fluoro, 3-chloro, 4-chloro, 2, 3-dichloro, 3, 4-dichloro, 4-n-propyl, 2-methoxy or 4-methoxy.
4. The process according to claim 3, wherein the amount ratio of the compound represented by the formula (II) to the ethyl 2-methylacetoacetate is 1:1 to 1:1.5 in the synthesis of the compound represented by the formula (III) in the step 1).
5. The process according to claim 3, wherein the mass ratio of the compound represented by the formula (III) to the Lawsen agent is 1:0.5 to 1:1 when the compound represented by the formula (IV) is synthesized in the step 2).
6. The process according to claim 3, wherein the ratio of the compound of the formula (IV) to the compound of the formula (V) is 1:1 to 1:1.5.
7. Use of a sulfur-containing quinoline compound according to claim 1 or 2 for the preparation of a fungicide.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1034924A (en) * | 1988-01-29 | 1989-08-23 | 伊莱利利公司 | quinoline, quinazoline and cinnoline derivatives |
| JPH0641117A (en) * | 1992-07-24 | 1994-02-15 | Mitsui Toatsu Chem Inc | Pyrimidinylthioquinoline derivative, its production and agricultural and horticultural fungicide containing the derivative as active component |
| CN115124463A (en) * | 2022-07-01 | 2022-09-30 | 浙江工业大学 | Substituted quinoline compound and preparation method and application thereof |
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2022
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1034924A (en) * | 1988-01-29 | 1989-08-23 | 伊莱利利公司 | quinoline, quinazoline and cinnoline derivatives |
| JPH0641117A (en) * | 1992-07-24 | 1994-02-15 | Mitsui Toatsu Chem Inc | Pyrimidinylthioquinoline derivative, its production and agricultural and horticultural fungicide containing the derivative as active component |
| CN115124463A (en) * | 2022-07-01 | 2022-09-30 | 浙江工业大学 | Substituted quinoline compound and preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 唐除痴: "《有机合成中的有机磷试剂》", 30 November 1992, 南开大学出版社, pages: 16 * |
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