CN114516844A - Quinoxaline derivative, preparation method and application - Google Patents
Quinoxaline derivative, preparation method and application Download PDFInfo
- Publication number
- CN114516844A CN114516844A CN202210056562.2A CN202210056562A CN114516844A CN 114516844 A CN114516844 A CN 114516844A CN 202210056562 A CN202210056562 A CN 202210056562A CN 114516844 A CN114516844 A CN 114516844A
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- Prior art keywords
- quinoxaline
- oxy
- preparation
- chloro
- methyl
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- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000004308 thiabendazole Substances 0.000 description 1
- 235000010296 thiabendazole Nutrition 0.000 description 1
- WJCNZQLZVWNLKY-UHFFFAOYSA-N thiabendazole Chemical compound S1C=NC(C=2NC3=CC=CC=C3N=2)=C1 WJCNZQLZVWNLKY-UHFFFAOYSA-N 0.000 description 1
- 229960004546 thiabendazole Drugs 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/44—Benzopyrazines 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 carbon atoms of the hetero ring
-
- 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
- A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
-
- 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
Abstract
The invention relates to the technical field of pesticide synthesis, in particular to quinoxaline derivatives, a preparation method and application thereof. According to the invention, a series of quinoxaline derivatives are synthesized by structurally modifying an active quinoxaline structure. The quinoxaline derivative prepared by the invention is proved to have good activity of inhibiting plant pathogenic bacteria (bacteria and fungi) by the activity test of resisting the plant pathogenic bacteria on the synthesized quinoxaline derivative, and can be used for preparing a medicament for sterilization.
Description
Technical Field
The invention relates to the technical field of pesticide synthesis, in particular to quinoxaline derivatives, a preparation method and application thereof.
Background
The quinoxaline derivative is a nitrogen-containing heterocyclic compound, is an important chemical intermediate, plays an important role in the design and synthesis of novel heterocyclic compounds, and has important significance for the discovery of medicaments. A large number of literature reports show that the quinoxaline derivative has broad-spectrum biological activity, such as antibiosis, antivirus, antitumor, antituberculosis and the like. Has certain research and application values, and people have more and more researches on the novel medical device in recent years.
In 2001, a series of 2-arylaminoquinoxalines were designed and synthesized by Rangisetty et al (Rangisetty J.B., Gupta C.N., Prasad A.L., et al.J.pharm. Pharmacol.,2001,53, 1409-one 1413.). All compounds were tested for antimalarial activity. Wherein the partial compound has certain antimalarial activity at 75 mg/kg.
In 2005, Zhao Cui Hua, etc. (Zhao Cui Hua, Chen Yi, Ding Jian, etc., pharmaceutical bulletin 2005,40,814-819.) designed and synthesized a series of quinoxaline antitumor drugs, and preliminary in vitro antitumor activity tests showed that 1 × 10-4At mol/L concentration, the antitumor activity of part of compounds is equivalent to that of XK 469.
In 2013, a series of quinoxaline compounds were synthesized by Parhi et al (Parhi A K., Zhang Y Z., Saionz K W., et al, Bioorg. Med. chem. Lett.,2013,23, 4968-4974), and antibacterial activity studies of 2 species of Staphylococcus aureus and 2 species of enterococcus faecalis were performed on the synthesized compounds. The results show that the MICs of one compound to methicillin-resistant staphylococcus aureus (MRSA) and methicillin-sensitive staphylococcus aureus (MSSA) are both 0.5 mu mol/L, which is superior to the inhibitory concentrations of vancomycin to MRSA and MSSA (2 mu mol/L and 1 mu mol/L).
In 2017, Ibrahim et al (Ibrahim M K., Eissa I H., Abdallah.E., et al.Bioorgan.Med.chem.,2017,25, 1496-one 1513.) introduce sulfonylurea or sulfonylthiourea into the backbone of quinoxaline, and the target compound was tested for anti-hyperglycemic activity. Tests show that the target compound shows significant antihyperglycemic activity.
In 2019, Mixo et al (Mixo A.S., Lerato R., Dikgale M., et al, molecules,2019,24,407.) synthesized a group of quinoxaline derivatives with wide biological activity, which have targeting and selective anti-cancer drug activity, and some compounds show the ability to inhibit cell viability, stimulate the generation of active oxygen, and induce apoptosis of A549 lung cancer cells.
In conclusion, the quinoxaline has a unique structure, has resource advantages in the research and application of medicines, is widely applied in medicines, has a small amount of commercialized medicaments in the aspect of pesticides, and has less application in the aspect of antibiosis. Therefore, the quinoxaline derivative, the preparation method and the application of resisting plant germs have important practical significance.
Disclosure of Invention
In view of the above, the invention provides quinoxaline derivatives, a preparation method and uses thereof. The experimental result of the invention shows that the quinoxaline derivative has a certain inhibiting effect on plant germs, wherein part of target compounds show excellent activity on resisting the plant germs, can be used as a potential plant germ resisting medicine, and has better application prospect.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a quinoxaline derivative, the structure of which is shown as formula I:
wherein R is1Selected from hydrogen, chlorine; and/or
R2One or more selected from methyl, alkoxy, nitro, cyano or halogen.
In some embodiments of the invention, in the quinoxaline derivative,
the methyl group includes a 2-methyl group; and/or
The alkoxy group includes 3-methoxy; and/or
The nitro group includes a 4-nitro group; and/or
The halogen comprises one or more of 2, 4-dichloro, 2-fluoro, 2-chloro, 3-fluoro, 4-chloro or 2-chloro-6-fluoro; and/or
The cyano group includes a 4-cyano group.
In some embodiments of the invention, the quinoxaline derivative comprises:
R1is H, R2Is 2, 4-dichloro; and/or
R1Is H, R2Is 4-nitro; and/or
R1Is H, R2Is 2-methyl; and/or
R1Is H, R2Is 2-fluoro; and/or
R1Is H, R2Is 3-methoxy; and/or
R1Is H, R2Is 2-chloro; and/or
R1Is H, R2Is 3-fluoro; and/or
R1Is H, R2Is 4-chloro; and/or
R1Is H, R2Is 2-chloro-6-fluoro; and/or
R1Is H, R2Is 4-cyano; and/or
R1Is Cl, R2Is 2, 4-dichloro; and/or
R1Is Cl, R2Is 4-nitro; and/or
R1Is Cl, R2Is 2-methyl; and/or
R1Is Cl, R2Is 2-fluoro; and/or
R1Is Cl, R2Is 3-methoxy; and/or
R1Is Cl, R2Is 2-chloro; and/or
R1Is Cl, R2Is 3-fluoro; and/or
R1Is Cl, R2Is 4-chloro; and/or
R1Is Cl, R2Is 2-chloro-6-fluoro; and/or
R1Is Cl, R2Is 4-cyano.
The invention also provides a preparation method of the quinoxaline derivative, which comprises the following steps:
step 1: substituted o-phenylenediamine and glyoxylic acid are used as raw materials, and ethanol (CH)3CH2OH) is used as a solvent, and the intermediate substituted 2-hydroxyquinoxaline is prepared by refluxing; then using N, N-Dimethylformamide (DMF) as solvent, and using substituted 2-hydroxyquinoxaline through POCl3After chlorination, substituted 2-chloroquinoxaline is prepared;
step 2: acetone as solvent, cesium carbonate (Cs)2CO3) The substituted 2-chloroquinoxaline reacts with methyl paraben to prepare 4- (quinoxaline-2-oxyl) methyl benzoate as a catalyst;
and step 3: carrying out reflux reaction on the 4- (quinoxaline-2-oxy) methyl benzoate by KOH and tetrahydrofuran to prepare 4- (quinoxaline-2-oxy) benzoic acid;
and 4, step 4: taking the 4- (quinoxaline-2-oxy) benzoic acid and substituted benzyl chloride as raw materials, K2CO3Is used as a catalyst, and acetonitrile is used as a solvent to prepare the quinoxaline derivative.
In addition, the invention also provides a bacteriostatic agent or a bactericide, which comprises the quinoxaline derivative or the quinoxaline derivative prepared by the preparation method, and acceptable auxiliary materials or auxiliary agents.
In some embodiments of the present invention, the formulation of the bacteriostatic or bactericidal agent includes one or more of emulsifiable concentrate, wettable powder, suspension, powder, soluble powder, aqueous solution, water dispersible granule, smoke agent, granule, seed coating agent, dry seed coating agent, wet seed coating agent or coating agent.
The invention also provides the quinoxaline derivative, the quinoxaline derivative prepared by the preparation method, and the application of the bacteriostatic agent or the bactericide in resisting plant pathogenic bacteria.
In some embodiments of the invention, the pathogenic bacteria comprise bacteria and/or fungi.
In some embodiments of the invention, the bacteria comprise one or more of bacterial fruit blotch of melon (Ac), bacterial wilt of tomato (Rs), bacterial blight of rice (Xoo), bacterial soft rot of potato (Pcb), bacterial black spot of mango (Xcm).
In some embodiments of the invention, the fungus comprises one or more of alternaria kii (AB), fusarium moniliforme (FF), Fusarium Oxysporum (FO), colletotrichum Capsici (CT), Phytophthora Capsici (PC), pectomycinia formosana (CG), Rhizoctonia Solani (RS), Fusarium Graminearum (FG), Phytophthora Sojae (PS), phytophthora nicotianae (PP), Botrytis Cinerea (BC), or Phytophthora Litchi (PL).
According to the invention, a series of quinoxaline derivatives are synthesized by structurally modifying an active quinoxaline structure.
The biological activity test result of the anti-plant pathogenic bacteria shows that the compound provided by the invention has certain inhibitory activity on melon bacterial fruit blotch pathogen (Ac), tomato bacterial wilt (Rs), rice bacterial leaf blight (Xoo), potato soft rot pathogen (Pcb) and mango bacterial angular leaf spot pathogen (Xcm). Wherein, when the concentration is 200 mug/mL, the inhibition rate of the compound I11 on Ac (bacterial fruit blotch of melon) is 86.2 percent, which is better than the control drugs TC (57.6 percent) and BT (41.0 percent). The inhibition rate of compound I15 on Pcb (potato soft rot) is 72.6%, which is better than that of control drugs TC (51.0%) and BT (49.6%). The inhibition rates of the compounds I2 and I3 on Rs (ralstonia solanacearum) are 71.3 percent and 70.4 percent respectively, and are superior to those of the control drugs TC (66.0 percent) and BT (42.3 percent). The inhibition effect of the compounds I16 and I17 on Xcm (mango bacterial alternaria alternata) is 75.1 percent and 74.2 percent respectively, which are superior to the control drugs TC (67.8 percent) and BT (46.8 percent).
The activity test result of the anti-plant pathogenic fungi shows that the inhibition rates of the compound I11 on FF (fusarium moniliforme), PS (phytophthora sojae) and PP (phytophthora nicotianae) are 89.3, 89.9 and 89.3% respectively at the concentration of 100 mu g/mL, and are all superior to those of azoxystrobin (76.4, 55.7 and 77.1%) serving as a control drug. The inhibition rates of the compounds I10 and I20 on RS (Rhizoctonia solani) are 89.5 percent and 95.1 percent respectively, which are better than those of the control azoxystrobin (76.4 percent).
The experimental activity data show that the quinoxaline derivative has a certain inhibiting effect on plant germs, wherein part of target compounds show excellent activity on resisting the plant germs, can be used as a potential plant germ resisting medicine, and has a good application prospect.
Detailed Description
The invention discloses quinoxaline derivatives, a preparation method and application thereof, and can be realized by appropriately improving process parameters by a person skilled in the art by referring to the content. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.
One of the technical schemes of the invention is as follows: a quinoxaline-containing derivative is provided, the structural formula is shown as formula I:
wherein R is1Hydrogen and chlorine; r2Is one or more of methyl, alkoxy, nitro and halogen.
Preferably, R is1The radical is quinoxaline benzene ring, the 6-position of which contains a hydrogen atom or a chlorine atom, the radical R2The radical is one or more of methyl, alkoxy, nitro and halogen atoms.
The second technical scheme of the invention is as follows: there is provided a method for preparing the above quinoxaline derivative, comprising the steps of:
(1) substituted o-phenylenediamine and glyoxylic acid are used as raw materials, and ethanol (CH)3CH2OH) is used as a solvent, and the intermediate substituted 2-hydroxyquinoxaline is prepared by refluxing; then N, N-Dimethylformamide (DMF) is used as solvent, substituted 2-hydroxyquinoxaline is treated by POCl3After chlorination, substituted 2 is obtained-chloroquinoxaline;
(2) acetone as solvent, cesium carbonate (Cs)2CO3) As a catalyst, substituted 2-chloroquinoxaline reacts with methyl paraben to prepare 4- (quinoxaline-2-oxy) methyl benzoate;
(3)4- (quinoxaline-2-oxy) benzoic acid methyl ester is subjected to reflux reaction of KOH and tetrahydrofuran to prepare 4- (quinoxaline-2-oxy) benzoic acid;
(4) using 4- (quinoxaline-2-oxy) benzoic acid and substituted benzyl chloride as raw materials, K2CO3Is used as a catalyst, acetonitrile is used as a solvent, and a series of quinoxaline derivatives are prepared.
Preferably, the substituted o-phenylenediamine in the step (1) and glyoxylic acid are reacted in an absolute ethanol solvent, and the chlorinating agent in the step (1) is POCl3The solvent is also POCl3DMF is the catalyst.
The step (1) of the invention comprises two steps of reaction, the second step is POCl3The hydroxyl group is chlorinated, and the reaction process is as follows:
preferably, the reaction of said step (2) is carried out in an acetone solvent.
The reaction process of step (2) of the invention is as follows:
the reaction process of step (3) of the present invention is as follows:
preferably, the reaction of step (4) is carried out by heating at 90 ℃.
The reaction process of step (4) of the present invention is as follows:
the third technical scheme of the invention is as follows: provides an application of the quinoxaline derivative in preparing phytopathogen.
The invention has the following beneficial technical effects:
according to the invention, a series of quinoxaline derivatives are synthesized by structurally modifying an active quinoxaline structure. The quinoxaline derivative prepared by the invention is proved to have good activity of inhibiting plant pathogenic bacteria (bacteria and fungi) by the activity test of resisting the plant pathogenic bacteria on the synthesized quinoxaline derivative, and can be used for preparing a medicament for sterilization.
For numerical ranges in this disclosure, it is understood that each intervening value, between the upper and lower limit of that range, is also specifically disclosed. Every smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
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. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention.
As used herein, the terms "comprising," "including," "having," "containing," and the like are open-ended terms that mean including, but not limited to.
The quinoxaline derivative, the preparation method and the application thereof provided by the invention have the advantages that the used raw materials and reagents can be purchased from the market.
The invention is further illustrated by the following examples:
example 12, 4-Dichlorobenzyl 4- (quinoxaline-2-oxy) benzoate (title compound I1) was prepared as follows:
(1) preparation of 2-chloroquinoxaline (intermediate 1):
a100 mL round bottom flask was charged with 2.0g (18.49mmol) o-phenylenediamine and 30mL CH3CH2After warming to 60 ℃ OH, 1.51g (20.34mmol) of glyoxylic acid was added slowly and the reaction was followed by TLC (petroleum ether: ethyl acetate 8:1, V/V). After the reaction is stopped, the reaction solution is decompressed and concentrated, and then is dried to obtain the 2-hydroxyquinoxaline. A100 mL round-bottom flask was charged with 2.0g (13.68mmol) of 2-hydroxyquinoxaline and 10.49g (68.42mmol) of POCl3DMF (1mL) was added, the reaction was refluxed at 90 ℃ and followed by TLC (petroleum ether: ethyl acetate: 5:1, V/V). After the reaction was stopped, a precipitate was formed by pouring into ice water, and a brown solid (intermediate 1) was obtained by suction filtration. Yield: 71 percent.
(2) Preparation of methyl 4- (quinoxaline-2-oxy) benzoate (intermediate 2):
2.00g (12.15mmol) of 2-chloroquinoxaline (intermediate 1), 2.22g (14.58mmol) of methyl p-hydroxybenzoate, 4.75g (14.58mmol) of cesium carbonate and 30mL of acetone were sequentially added to a 100mL round-bottomed flask, stirred at room temperature for 48h, and the reaction was followed by TLC (petroleum ether: ethyl acetate ═ 8:1, V/V). After the reaction was stopped, concentration under reduced pressure, addition of 40mL of distilled water, extraction with ethyl acetate three times, combination of organic layers, concentration under reduced pressure to obtain a crude product of methyl 4- (quinoxaline-2-oxy) benzoate (intermediate 2), yield: 58 percent.
(3) Preparation of 4- (quinoxaline-2-oxy) benzoic acid (intermediate 3):
to a 100mL three-necked round-bottomed flask were added methyl 4- (quinoxaline-2-oxy) benzoate (intermediate 2)2.0g (7.14mmol), KOH 1.2g (21.41mmol) and 40mL of tetrahydrofuran in this order, and the reaction was heated to 70 ℃ under reflux and monitored by TLC (ethyl acetate). After the reaction is stopped, cooling to room temperature, adjusting the pH value to 1 by using hydrochloric acid under the ice bath condition, separating out white solid, performing suction filtration, and drying to obtain 4- (quinoxaline-2-oxyl) benzoic acid (an intermediate 3), wherein the yield is as follows: and 63 percent.
(4) Preparation of 2, 4-dichlorobenzyl 4- (quinoxaline-2-oxy) benzoate (target compound I1):
in a 100mL single-neck flask were charged 0.5g (1.88mmol) of 4- (quinoxaline-2-oxy) benzoic acid (intermediate 3), K2CO30.35g (2.56mmol) and 40mL of acetonitrile were stirred with heatingAfter stirring for 0.5 to 1 hour, 0.33g (1.71mmol) of 2, 4-dichlorobenzyl chloride is added, the reaction is followed by TLC (petroleum ether: ethyl acetate: 8:1, V/V), after the reaction is stopped, the mixture is poured into 100mL of water, a white precipitate is precipitated, after the solution is clarified, the crude product is obtained by suction filtration, and the crude product is purified by column chromatography (petroleum ether: ethyl acetate: 30:1, V/V) to obtain a white solid (the target compound I1) with yield: 61 percent.
Example 24-Nitrobenzyl 4- (quinoxaline-2-oxy) benzoate (title compound I2) was prepared as follows:
(1) preparation of 2-chloroquinoxaline (intermediate 1):
as in step (1) of example 1.
(2) Preparation of methyl 4- (quinoxaline-2-oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- (quinoxaline-2-oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 4-nitrobenzyl 4- (quinoxaline-2-oxy) benzoate (target compound I2):
the procedure of step (4) in example 1 was followed, except for replacing 2, 4-dichlorobenzyl chloride with an equimolar amount of 4-nitrobenzyl chloride. Yield: 58 percent.
Example 32-Methylbenzyl 4- (quinoxaline-2-oxy) benzoate (title compound I3) was prepared as follows:
(1) preparation of 2-chloroquinoxaline (intermediate 1):
as in step (1) of example 1.
(2) Preparation of methyl 4- (quinoxaline-2-oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- (quinoxaline-2-oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 2-methylbenzyl 4- (quinoxaline-2-oxy) benzoate (target compound I3):
the procedure of (4) in example 1 was repeated, except that 2, 4-dichlorobenzyl chloride was replaced with 2-methylbenzyl chloride. Yield: 59 percent.
Example 42-Fluorobenzyl 4- (quinoxaline-2-oxy) benzoate (title compound I4) was prepared as follows:
(1) preparation of 2-chloroquinoxaline (intermediate 1):
as in step (1) of example 1.
(2) Preparation of methyl 4- (quinoxaline-2-oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- (quinoxaline-2-oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 2-fluorobenzyl 4- (quinoxaline-2-oxy) benzoate (target compound I4):
the procedure was as in step (4) of example 1, except for replacing 2, 4-dichlorobenzyl chloride with an equimolar amount of 2-fluorobenzyl chloride. Yield: 67%.
Example 53-Methoxybenzyl 4- (quinoxaline-2-oxy) benzoate (title compound I5) was prepared as follows:
(1) preparation of 2-chloroquinoxaline (intermediate 1):
as in step (1) of example 1.
(2) Preparation of methyl 4- (quinoxaline-2-oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- (quinoxaline-2-oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 3-methoxybenzyl 4- (quinoxaline-2-oxy) benzoate (target compound I5):
the procedure is as in step (4) of example 1, except that 2, 4-dichlorobenzyl chloride is replaced with an equimolar amount of 3-methoxybenzyl chloride. Yield: 49 percent.
Example 62-chlorobenzyl 4- (quinoxaline-2-oxy) benzoate (target compound I6) the preparation process is as follows:
(1) preparation of 2-chloroquinoxaline (intermediate 1):
as in step (1) of example 1.
(2) Preparation of methyl 4- (quinoxaline-2-oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- (quinoxaline-2-oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 2-chlorobenzyl 4- (quinoxaline-2-oxy) benzoate (target compound I6):
the procedure was as in step (4) of example 1, except for replacing 2, 4-dichlorobenzyl chloride with an equimolar amount of 2-chlorobenzyl chloride. Yield: 52 percent.
Example 73-Fluorobenzyl 4- (quinoxaline-2-oxy) benzoate (title compound I7) was prepared as follows:
(1) preparation of 2-chloroquinoxaline (intermediate 1):
as in step (1) of example 1.
(2) Preparation of methyl 4- (quinoxaline-2-oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- (quinoxaline-2-oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 3-fluorobenzyl 4- (quinoxaline-2-oxy) benzoate (target compound I7):
the procedure was as in step (4) of example 1, except for replacing 2, 4-dichlorobenzyl chloride with an equimolar amount of 3-fluorobenzyl chloride. Yield: and 64 percent.
Example 84-chlorobenzyl 4- (quinoxaline-2-oxy) benzoate (title compound I8) was prepared as follows:
(1) preparation of 2-chloroquinoxaline (intermediate 1):
as in step (1) of example 1.
(2) Preparation of methyl 4- (quinoxaline-2-oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- (quinoxaline-2-oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 4-chlorobenzyl 4- (quinoxaline-2-oxy) benzoate (target compound I8):
the procedure was as in step (4) of example 1, except for replacing 2, 4-dichlorobenzyl chloride with an equimolar amount of 4-chlorobenzyl chloride. Yield: 73 percent.
Example 92-chloro-6-fluorobenzyl 4- (quinoxaline-2-oxy) benzoate (title compound I9) was prepared as follows:
(1) preparation of 2-chloroquinoxaline (intermediate 1):
as in step (1) of example 1.
(2) Preparation of methyl 4- (quinoxaline-2-oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- (quinoxaline-2-oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 2-chloro-6-fluorobenzyl 4- (quinoxaline-2-oxy) benzoate (target compound I9):
the procedure of step (4) in example 1 was repeated, except that 2, 4-dichlorobenzyl chloride was replaced with an equimolar amount of 2-chloro-6-fluorobenzyl chloride. Yield: 54 percent.
Example 104-Cyanobenzyl 4- (quinoxaline-2-oxy) benzoate (title compound I10) was prepared as follows:
(1) preparation of 2-chloroquinoxaline (intermediate 1):
as in step (1) of example 1.
(2) Preparation of methyl 4- (quinoxaline-2-oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- (quinoxaline-2-oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 4-cyanobenzyl 4- (quinoxaline-2-oxy) benzoate (target compound I10):
the procedure is as in step (4) of example 1, except that 2, 4-dichlorobenzyl chloride is replaced with an equimolar amount of 4-cyanobenzyl chloride. Yield: 91 percent.
Example 112, 4-dichlorobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I11) was prepared as follows:
(1) preparation of 2, 6-dichloroquinoxaline (intermediate 1):
the procedure is as in step (1) of example 1, except that 4-chloro-o-diphenylamine is used in an equimolar amount as a starting material.
(2) Preparation of methyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- ((6-chloroquinoxalin-2-yl) oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 2, 4-dichlorobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (target compound I11):
as in step (4) of example 1. Yield: 62 percent.
Example 124-Nitrobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I12) was prepared as follows:
(1) preparation of 2, 6-dichloroquinoxaline (intermediate 1):
the procedure is as in step (1) of example 1, except that 4-chloro-o-diphenylamine is used in an equimolar amount as a starting material.
(2) Preparation of methyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- ((6-chloroquinoxalin-2-yl) oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 4-nitrobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I12):
the procedure was as in step (4) of example 1, except for replacing 2, 4-dichlorobenzyl chloride with an equimolar amount of 4-nitrobenzyl chloride. Yield: 51 percent.
Example 132-methylbenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I13) was prepared as follows:
(1) preparation of 2, 6-dichloroquinoxaline (intermediate 1):
the procedure is as in step (1) of example 1, except that 4-chloro-o-diphenylamine is used in an equimolar amount as a starting material.
(2) Preparation of methyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- ((6-chloroquinoxalin-2-yl) oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 2-methylbenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I13):
the procedure was as in step (4) of example 1, except that 2, 4-dichlorobenzyl chloride was replaced with an equimolar amount of 2-methylbenzyl chloride. Yield: 36 percent.
Example 142-Fluorobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I14) was prepared as follows:
(1) preparation of 2, 6-dichloroquinoxaline (intermediate 1):
the procedure is as in step (1) of example 1, except that 4-chloro-o-diphenylamine is used in an equimolar amount as a starting material.
(2) Preparation of methyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- ((6-chloroquinoxalin-2-yl) oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 2-fluorobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I14):
the procedure was as in step (4) of example 1, except for replacing 2, 4-dichlorobenzyl chloride with an equimolar amount of 2-fluorobenzyl chloride. Yield: 75 percent.
Example 153-Methoxybenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I15) was prepared as follows:
(1) preparation of 2, 6-dichloroquinoxaline (intermediate 1):
the procedure of step (1) in example 1 was followed, except that 4-chloro-o-diphenylamine was used in an equimolar amount as a starting material.
(2) Preparation of methyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- ((6-chloroquinoxalin-2-yl) oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 3-methoxybenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I15):
the procedure is as in step (4) of example 1, except that 2, 4-dichlorobenzyl chloride is replaced with an equimolar amount of 3-methoxybenzyl chloride. Yield: 80 percent.
Example 162-chlorobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I16) was prepared as follows:
(1) preparation of 2, 6-dichloroquinoxaline (intermediate 1):
the procedure is as in step (1) of example 1, except that 4-chloro-o-diphenylamine is used in an equimolar amount as a starting material.
(2) Preparation of methyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- ((6-chloroquinoxalin-2-yl) oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 2-chlorobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I16):
the procedure was as in step (4) of example 1, except for replacing 2, 4-dichlorobenzyl chloride with an equimolar amount of 2-chlorobenzyl chloride. Yield: and 69 percent.
Example 173-Fluorobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I17) was prepared as follows:
(1) preparation of 2, 6-dichloroquinoxaline (intermediate 1):
the procedure is as in step (1) of example 1, except that 4-chloro-o-diphenylamine is used in an equimolar amount as a starting material.
(2) Preparation of methyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- ((6-chloroquinoxalin-2-yl) oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 3-fluorobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (target compound I17):
the procedure was as in step (4) of example 1, except for replacing 2, 4-dichlorobenzyl chloride with an equimolar amount of 3-fluorobenzyl chloride. Yield: 53 percent.
Example 184-chlorobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I18) was prepared as follows:
(1) preparation of 2, 6-dichloroquinoxaline (intermediate 1):
the procedure is as in step (1) of example 1, except that 4-chloro-o-diphenylamine is used in an equimolar amount as a starting material.
(2) Preparation of methyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- ((6-chloroquinoxalin-2-yl) oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 4-chlorobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I18):
the procedure was as in step (4) of example 1, except for replacing 2, 4-dichlorobenzyl chloride with an equimolar amount of 4-chlorobenzyl chloride. Yield: 48 percent.
Example 192-chloro-6-fluorobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I19) was prepared as follows:
(1) preparation of 2, 6-dichloroquinoxaline (intermediate 1):
the procedure is as in step (1) of example 1, except that 4-chloro-o-diphenylamine is used in an equimolar amount as a starting material.
(2) Preparation of methyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- ((6-chloroquinoxalin-2-yl) oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 2-chloro-6-fluorobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (target compound I19):
the procedure of step (4) in example 1 was repeated, except that 2, 4-dichlorobenzyl chloride was replaced with an equimolar amount of 2-chloro-6-fluorobenzyl chloride. Yield: and 55 percent.
Example 204-Cyanobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I20) was prepared as follows:
(1) preparation of 2, 6-dichloroquinoxaline (intermediate 1):
the procedure is as in step (1) of example 1, except that 4-chloro-o-diphenylamine is used in an equimolar amount as a starting material.
(2) Preparation of methyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (intermediate 2):
as in step (2) of example 1.
(3) Preparation of 4- ((6-chloroquinoxalin-2-yl) oxy) benzoic acid (intermediate 3):
as in step (3) of example 1.
(4) Preparation of 4-cyanobenzyl 4- ((6-chloroquinoxalin-2-yl) oxy) benzoate (title compound I20):
the procedure is as in step (4) of example 1, except that 2, 4-dichlorobenzyl chloride is replaced with an equimolar amount of 4-cyanobenzyl chloride. Yield: 45 percent.
The physicochemical properties and mass spectrum data of the synthesized quinoxaline derivative are shown in Table 1, and the nuclear magnetic resonance hydrogen spectrum (1H NMR), carbon spectrum (13C NMR) and fluorine Spectroscopy (19F NMR) data are shown in table 2.
TABLE 1 physicochemical Properties of the example Compounds I1-I20
TABLE 2 NMR data for target compounds I1-I20
Experimental example 1 test against plant pathogenic bacteria:
(1) test method
A96-well plate method is adopted, the in-vitro inhibitory activity of a target compound on melon bacterial fruit blotch (Ac), tomato ralstonia solanacearum (Rs), rice bacterial leaf blight (Xoo), potato soft rot (Pcb) and mango bacterial black spot (Xcm) is tested under the concentration of 200 mug/mL and 100 mug/mL, the control agents are Bismerthiazol (BT) and benziothiazolinone (TC), and the specific operation steps are as follows:
preparing bacterial liquid: selecting a single colony in a liquid culture medium (different bacteria adopt different culture media), placing the single colony in a shaking table at 28 ℃ and 180r/min for culturing until the logarithmic growth phase, taking two tubes of 2mL bacteria liquid, centrifuging for 5min under the condition that the rotating speed is 6000rpm, removing the culture medium liquid, adding 2mL sterile water, uniformly mixing the bacteria and the water, taking one tube for measuring under the wavelength of 600nm of an ultraviolet spectrophotometer, adjusting the absorbance value to be 0.6, and storing the other tube for later use. Preparing a liquid medicine: 1mg of test drug was dissolved in 100. mu.L DMSO and the final concentrations were made up to 200. mu.g/mL and 100. mu.g/mL of drug-containing medium in liquid medium (different bacteria for different media). 190 mu L of drug-containing culture medium and 10 mu L of prepared bacterial liquid are added into a 96-well plate, the negative control is culture medium with bacteria and without liquid, the positive control is commercial medicament of thiabendazole and bismerthiazol, and the culture medium with the bacteria and without the bacteria is used as blank control. Culturing 96-well plate in shaker at 28 deg.C and 180r/min until the negative control OD value is 0.6-0.8, and measuring the OD of all bacteria liquid with enzyme-labeling instrument600nmValues were determined and the inhibition of test bacteria by the test drug was calculated using SPSS. 3 replicates were set for each treatment and 3 replicates for each experiment. The inhibition was calculated as follows:
correcting OD600Value-bacteria-containing Medium OD600Sterile Medium OD600
Inhibition ratio (%) (control medium OD after correction)600Corrected drug-containing Medium OD600) Corrected OD value of control medium liquid is multiplied by 100%.
(2) Results of biological Activity test against plant pathogenic bacteria
TABLE 3 bacteriostatic Activity (% inhibition) of the Compounds prepared in examples 1-20a
Remarking:aaverage three replicates;bbismerthiazol and copper thielavone (20% wettable powder) were used as positive controls.
As can be seen from Table 3, all compounds have certain inhibitory activity against bacterial fruit blotch of melon (Ac), bacterial wilt of tomato (Rs), bacterial blight of rice (Xoo), soft rot of potato (Pcb) and bacterial angular leaf spot of mango (Xcm). Wherein, when the concentration is 200 mug/mL, the inhibition rate of the compound I11 on Ac (bacterial fruit blotch of melon) is 86.2 percent, which is better than the control drugs TC (57.6 percent) and BT (41.0 percent). The inhibition rate of compound I15 on Pcb (potato soft rot) is 72.6%, which is better than that of control drugs TC (51.0%) and BT (49.6%). The inhibition rates of the compounds I2 and I3 on Rs (ralstonia solanacearum) are 71.3 percent and 70.4 percent respectively, and are superior to those of the control drugs TC (66.0 percent) and BT (42.3 percent). The inhibition effect of the compounds I16 and I17 on Xcm (mango bacterial alternaria alternata) is 75.1 percent and 74.2 percent respectively, which are superior to the control drugs TC (67.8 percent) and BT (46.8 percent).
Test example 2 activity test against plant pathogenic fungi:
(1) test method
In vitro activity evaluation is carried out on twelve plant pathogenic fungi, namely, cabbage black spot pathogen (AB), strawberry fusarium moniliforme (FF), cucumber Fusarium Oxysporum (FO), pepper Colletotrichum (CT), Phytophthora Capsici (PC), pectorale blight (CG), rice sheath blight pathogen (RS), wheat scab (FG), soybean Phytophthora Sojae (PS), tobacco black shank pathogen (PP), tomato gray mold pathogen (BC) and Peronophythora Litchi (PL), by adopting a hypha growth rate method, and the commercial agent azoxystrobin is used as a positive control. The method comprises the following specific steps:
dissolving 3mg of test drug in 300 mu L of DMSO, adding 200 mu L of liquid medicine into 1980 mu L of melted PDA culture medium to prepare a drug-containing culture medium with a final concentration of 100 mu g/mL, uniformly pouring the drug-containing culture medium into three sterilized culture dishes, beating a 4.00mm fungus cake from fungus colonies after the fungus cake is solidified, placing the fungus cake at the center of the drug-containing culture dish, sealing a sealing film, placing a negative control medium which is a culture medium with bacteria and without liquid medicine, placing a positive control medium which is a commercial medicament carbendazim in an incubator at 28 ℃ for culturing for 2-6 days, measuring the diameter of the fungus colonies by adopting a cross method, and calculating the inhibition rate of the test drug on the test fungus by using SPSS. 3 replicates were set for each treatment and 3 replicates for each experiment. The inhibition rate was calculated as follows:
inhibition ratio I (%) ═ (C)tur-Ttur)/(Ctur-0.4)×100
CturControl colony diameter, i.e., DMSO-treated colony diameter;
Tturdiameter of the drug-treated colony;
0.4: the diameter of the fungus cake;
i, inhibition rate.
PDA culture medium: 200g of potato, 20g of glucose, 20g of agar and 1000mL of distilled water
Cutting peeled potatoes into blocks, putting the cut potatoes into 800mL of distilled water, boiling until the potatoes are cut up, filtering the cut potatoes with gauze, boiling the filtrate, 20g of glucose and 20g of agar again, uniformly mixing the filtrate, and adding the distilled water to a constant volume of 1000 mL.
(2) Results of biological Activity test against plant pathogenic fungi
TABLE 4
At the concentration of 100 mu g/mL, the inhibition rates of the compound I11 on FF (fusarium moniliforme), PS (phytophthora sojae) and PP (phytophthora nicotianae) are 89.3, 89.9 and 89.3% respectively, which are all superior to those of the azoxystrobin serving as a control drug (76.4, 55.7 and 77.1%). The inhibition rates of the compounds I10 and I20 on RS (Rhizoctonia solani) are 89.5 percent and 95.1 percent respectively, which are better than those of the control azoxystrobin (76.4 percent).
The experimental activity data show that the quinoxaline derivative has a certain inhibiting effect on plant germs, wherein part of target compounds show excellent activity on resisting the plant germs, can be used as a potential plant germ resisting medicine, and has a good application prospect.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. Quinoxaline derivatives characterized by the structure as shown in formula I:
wherein R is1Selected from hydrogen, chlorine; and/or
R2One or more selected from methyl, alkoxy, nitro, cyano or halogen.
2. The quinoxaline derivative according to claim 1,
the methyl group includes a 2-methyl group; and/or
The alkoxy group includes 3-methoxy; and/or
The nitro group includes a 4-nitro group; and/or
The halogen comprises one or more of 2, 4-dichloro, 2-fluoro, 2-chloro, 3-fluoro, 4-chloro or 2-chloro-6-fluoro; and/or
The cyano group includes a 4-cyano group.
3. The quinoxaline derivative according to claim 1 or 2, which comprises:
R1is H, R2Is 2, 4-dichloro; and/or
R1Is H, R2Is 4-nitro; and/or
R1Is H, R2Is 2-methyl; and/or
R1Is H, R2Is 2-fluoro; and/or
R1Is H, R2Is 3-methoxy; and/or
R1Is H, R2Is 2-chloro; and/or
R1Is H, R2Is 3-fluoro; and/or
R1Is H, R2Is 4-chloro; and/or
R1Is H, R2Is 2-chloro-6-fluoro; and/or
R1Is H, R2Is 4-cyano; and/or
R1Is Cl, R2Is 2, 4-dichloro; and/or
R1Is Cl, R2Is 4-nitro; and/or
R1Is Cl, R2Is 2-methyl; and/or
R1Is Cl, R2Is 2-fluoro; and/or
R1Is Cl, R2Is 3-methoxy; and/or
R1Is Cl, R2Is 2-chloro; and/or
R1Is Cl, R2Is 3-fluoro; and/or
R1Is Cl, R2Is 4-chloro; and/or
R1Is Cl, R2Is 2-chloro-6-fluoro; and/or
R1Is Cl, R2Is a 4-cyano group.
4. A process for producing the quinoxaline derivative according to any one of claims 1 to 3, comprising the steps of:
step 1: substituted o-phenylenediamine and glyoxylic acid are used as raw materials, and ethanol (CH)3CH2OH) is used as a solvent, and the intermediate substituted 2-hydroxyquinoxaline is prepared by refluxing; then using N, N-Dimethylformamide (DMF) as solvent, and using substituted 2-hydroxyquinoxaline through POCl3After chlorination, substituted 2-chloroquinoxaline is prepared;
step 2: acetone as solvent, cesium carbonate (Cs)2CO3) As catalyst, the substituted 2-chloroquinoxaline and methyl parabenReacting to prepare 4- (quinoxaline-2-oxyl) methyl benzoate;
and step 3: carrying out reflux reaction on the 4- (quinoxaline-2-oxy) methyl benzoate by KOH and tetrahydrofuran to prepare 4- (quinoxaline-2-oxy) benzoic acid;
and 4, step 4: taking the 4- (quinoxaline-2-oxy) benzoic acid and substituted benzyl chloride as raw materials, K2CO3Is used as a catalyst, and acetonitrile is used as a solvent to prepare the quinoxaline derivative.
5. Bacteriostatic or bactericidal agent, characterized in that it comprises the quinoxaline derivative according to any one of claims 1 to 3 or the quinoxaline derivative prepared by the preparation method according to claim 4, and acceptable auxiliary materials or auxiliary agents.
6. The bacteriostatic or bactericidal agent according to claim 5, wherein the formulation thereof comprises one or more of emulsifiable concentrate, wettable powder, suspension, dust, soluble powder, aqueous solution, water dispersible granule, smoke agent, granule, seed coating agent, dry seed coating agent, wet seed coating agent or coating agent.
7. Use of the quinoxaline derivative according to any one of claims 1 to 3, the quinoxaline derivative obtained by the process according to claim 4, the bacteriostatic or bacteriocidal agent according to claim 5 or 6 for combating phytopathogens.
8. The use of claim 7, wherein the pathogenic bacteria comprise bacteria and/or fungi.
9. The use of claim 7 or 8, wherein the bacteria comprise one or more of bacterial fruit blotch of melon (Ac), bacterial wilt of tomato (Rs), bacterial blight of rice (Xoo), bacterial soft rot of potato (Pcb), bacterial black spot of mango (Xcm).
10. Use according to any one of claims 7 to 9, wherein the fungus comprises one or more of alternaria kii (AB), fusarium moniliforme (FF), fusarium oxysporum F.sp.cubense (FO), colletotrichum gloeosporioides (CT), Phytophthora Capsici (PC), pectinospora piricola (CG), Rhizoctonia Solani (RS), fusarium graminearum tritici (FG), Phytophthora Sojae (PS), phytophthora nicotianae (PP), Botrytis Cinerea (BC) or Phytophthora Lychnophora (PL).
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