CN109265448B - Tert-butyl-containing N-imidazole acetyl dihydroquinoxaline derivative, synthesis method and application thereof as bactericide - Google Patents
Tert-butyl-containing N-imidazole acetyl dihydroquinoxaline derivative, synthesis method and application thereof as bactericide Download PDFInfo
- Publication number
- CN109265448B CN109265448B CN201811361161.8A CN201811361161A CN109265448B CN 109265448 B CN109265448 B CN 109265448B CN 201811361161 A CN201811361161 A CN 201811361161A CN 109265448 B CN109265448 B CN 109265448B
- Authority
- CN
- China
- Prior art keywords
- tert
- derivative
- butyl
- azidoaniline
- hours
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Abstract
The invention provides a tert-butyl-containing N-imidazole acetyl dihydroquinoxaline derivative. The general formula is as follows (I)
Description
Technical Field
The invention relates to a tert-butyl-containing N-imidazole acetyl dihydroquinoxaline bactericide, a synthesis method and application thereof.
Background
The reduced yield of grains caused by crop diseases caused by various bacteria and fungi causes the problem of insufficient grain supply to a great extent. In order to solve the problem of people eating, the method improves the yield of grains and reduces the diseases of crops is urgent. The development of high-efficiency broad-spectrum bactericides is the first choice for solving the problems. Research and development of more novel bactericides with better antibacterial activity are the key for promoting the development of the bactericides. In the patent, we prepare a kind of N-imidazole acetyl dihydroquinoxaline bactericide containing tertiary butyl group with novel structure. The bactericide can effectively inhibit the growth of rice sheath blight fungus, wheat gibberella and Penicillium italicum.
Disclosure of Invention
The invention mainly aims to provide a tert-butyl-containing N-imidazole acetyl dihydroquinoxaline bactericide, a synthesis method and application thereof.
The invention provides a tert-butyl-containing N-imidazole acetyl dihydroquinoxaline fungicide (I):
wherein R in the formula is hydrogen, fluorine, chlorine, trifluoromethyl, methyl and the like. The position and the number of the substituent groups are not fixed.
The R is fluorine, the number of the R is two, the R is meta, and the structural formula of the R is as follows:
the preparation method for synthesizing the N-imidazole acetyl dihydroquinoxaline bactericide containing tert-butyl comprises the following specific steps:
(1) sequentially adding an o-azidoaniline derivative, an alpha-bromo-tert-butyl ketone derivative and potassium carbonate into a container filled with an organic solvent, reacting at 40-50 ℃ for 2-8 hours, adding diphenyl methyl phosphine, and reacting at 25-32 ℃ for 2-6 hours;
(2) after the reaction in the step (1) is finished, removing the organic solvent under reduced pressure, transferring the residue to a chloroform solution containing triphenylphosphine and iodine simple substances, adding imidazole acetic acid, reacting at 40-50 ℃ for 1-5 hours, after the reaction is finished, removing the organic solvent under reduced pressure, and performing column chromatography on the residue to obtain a compound 2 containing the N-imidazole acetyl dihydroquinoxaline derivative of the tert-butyl group;
the synthesis route is as follows:
in the step (1), the mol ratio of the o-azidoaniline derivative to the alpha-bromo-tert-butyl ketone derivative to the potassium carbonate to the diphenyl methylphosphine is 1: 0.1-3: 0.1-3: 0.1-3.
The molar ratio of triphenylphosphine, iodine simple substance and imidazole acetic acid in the step (2) to the o-azidoaniline derivative in the step (1) is 0.1-6: 0.1-6: 0.1-3: 1.
the o-azidoaniline derivative is any one of o-azidoaniline, 4-chloro-o-azidoaniline, 4-bromo-o-azidoaniline, 4-methyl-o-azidoaniline, 6-methyl-o-azidoaniline and 4, 6-dimethyl-o-azidoaniline.
The organic solvent in the steps (1) and (2) is chloroform. Chloroform, a useful solvent, is anhydrous and contains water, which results in a significant reduction in yield.
The invention has the following beneficial effects:
1. the invention provides a novel tert-butyl-containing N-imidazole acetyl dihydroquinoxaline derivative and a preparation method thereof.
2. The invention synthesizes a novel N-imidazole acetyl dihydroquinoxaline derivative containing tert-butyl, and the compound has certain effect on inhibiting fungi such as rice sheath blight fungus, wheat gibberella, penicillium italicum and the like, and is worthy of further development and research.
Detailed Description
The following examples are provided to further illustrate the preparation and utility of the compounds of formula (I) of this invention.
Instruments and reagents:
the melting point was measured by X4 type melting point apparatus (manufactured by Beijing third Optic instruments Co., Ltd.), and the thermometer was not corrected;1h NMR and13c NMR was measured using a Varian Mercury 400 model 400MHz NMR spectrometer or a Varian Mercury 600 model 600MHz NMR spectrometer using deuterated chloroform (CDCl)3) Or deuterated dimethyl sulfoxide (DMSO-d)6) Is a solvent, TMS is an internal standard; MS was determined using a finnigan trace mass spectrometer; elemental analysis was determined using a Vario EL III elemental analyzer; the reagent is chemically pure or analytically pure. The solvent toluene was dried by redistilling, and triethylamine was also treated by redistilling.
Example 1
To a 50mL flask were added o-azidoaniline 1a (1mmol), α -bromo-tert-butyl ketone (1.2mmol) and potassium carbonate (1.5mmol) and reacted at 45 ℃ in chloroform (20mL) as a reaction solvent, after 2 hours of reaction, diphenyl methylphosphine (1.5mmol) was added and reacted at 30 ℃ for 3 hours, after which the solvent chloroform was removed under reduced pressure, the residue was transferred to a chloroform (15mL) solution containing triphenylphosphine (2.5mmol) and iodine as a simple substance (2.5mmol), imidazole acetic acid (1.5mmol) was added and reacted at 45 ℃ for 2 hours, after completion of reaction, the solvent chloroform was removed under reduced pressure, and the residue was column-chromatographed to give 0.217g of the objective compound 2a, 73% yield.
Example 2
To a 5mL flask were added o-azidoaniline 1a (0.1mmol), α -bromo-tert-butyl ketone (0.12mmol) and potassium carbonate (0.15mmol) and reacted at 45 ℃ in chloroform (2mL) as a reaction solvent, after 2 hours of reaction, diphenylmethylphosphine (0.15mmol) was added and reacted at 30 ℃ for 3 hours, after which the solvent chloroform was removed under reduced pressure, the residue was transferred to a chloroform (1.5mL) solution containing triphenylphosphine (0.25mmol) and iodine (0.25mmol), imidazole acetic acid (0.15mmol) was added and reacted at 45 ℃ for 2 hours, after completion of reaction, the solvent chloroform was removed under reduced pressure, and the residue was subjected to column chromatography to give 0.023g of the objective compound 2a in 77% yield.
Example 3
After a 500mL flask was charged with o-azidoaniline 1a (10mmol), α -bromo-tert-butyl ketone (12mmol) and potassium carbonate (15mmol) and reacted at 45 ℃ in chloroform (200mL) as a reaction solvent for 2 hours, diphenylmethylphosphine (15mmol) was added and reacted at 30 ℃ for 3 hours, the solvent chloroform was removed under reduced pressure, the residue was transferred to a chloroform (150mL) solution containing triphenylphosphine (25mmol) and iodine (25mmol), imidazoleacetic acid (15mmol) was added and reacted at 45 ℃ for 2 hours, and after completion of the reaction, the solvent chloroform was removed under reduced pressure and column chromatography of the residue gave 2.02g of the objective compound 2a in 68% yield.
Example 4
To a 50mL flask were added o-azidoaniline 1a (1mmol), α -bromo-tert-butyl ketone (1.2mmol) and sodium carbonate (1.5mmol) and reacted at 45 ℃ in chloroform (20mL) as a reaction solvent, after 2 hours of reaction, diphenyl methylphosphine (1.5mmol) was added and reacted at 30 ℃ and after 3 hours of further reaction, chloroform was removed under reduced pressure, the residue was transferred to a chloroform (15mL) solution containing triphenylphosphine (2.5mmol) and iodine as a simple substance (2.5mmol), imidazole acetic acid (1.5mmol) was added and reacted at 45 ℃ for 2 hours, after completion of reaction, chloroform was removed under reduced pressure and column chromatography of the residue gave 0.163g of the objective compound 2a in 55% yield.
Example 5
In a 50mL flask were added 4-chloro-o-azidoaniline 1b (1mmol), α -bromo-tert-butyl ketone (1.2mmol) and potassium carbonate (1.5mmol) and reacted at 45 ℃ in chloroform (20mL) as a reaction solvent, and after 2 hours of reaction, diphenylmethylphosphine (1.5mmol) was added and reacted at 30 ℃ for 3 hours, and after removing the solvent chloroform under reduced pressure, the residue was transferred to a chloroform (15mL) solution containing triphenylphosphine (2.5mmol) and iodine (2.5mmol), and then imidazoleacetic acid (1.5mmol) was added and reacted at 45 ℃ for 2 hours, and after completion of reaction, the solvent chloroform was removed under reduced pressure, and the residue was subjected to column chromatography to give 0.228g of the objective compound 2b in 69% yield.
Example 7
In a 50mL flask were added 4-fluoro-o-azidoaniline 1c (1mmol), α -bromo-tert-butyl ketone (1.2mmol) and potassium carbonate (1.5mmol) and reacted at 45 ℃ in chloroform (20mL) as a reaction solvent, and after 2 hours of reaction, diphenylmethylphosphine (1.5mmol) was added and reacted at 30 ℃ for 3 hours, and after removing the solvent chloroform under reduced pressure, the residue was transferred to a chloroform (15mL) solution containing triphenylphosphine (2.5mmol) and iodine (2.5mmol), and then imidazoleacetic acid (1.5mmol) was added and reacted at 45 ℃ for 2 hours, and after completion of reaction, the solvent chloroform was removed under reduced pressure, and the residue was subjected to column chromatography to give 0.223g of the objective compound 2c in 71% yield.
Example 8
To a 50mL flask were added 4, 6-difluoro-o-azidoaniline 1d (1mmol), α -bromo-tert-butyl ketone (1.2mmol) and potassium carbonate (1.5mmol) and reacted at 45 ℃ in chloroform (20mL) as a reaction solvent, and after 2 hours of reaction, diphenylmethylphosphine (1.5mmol) was added and reacted at 30 ℃ for 3 hours, and after removing the solvent chloroform under reduced pressure, the residue was transferred to a chloroform (15mL) solution containing triphenylphosphine (2.5mmol) and iodine (2.5mmol), and then imidazoleacetic acid (1.5mmol) was added and reacted at 45 ℃ for 2 hours, and after completion of reaction, the solvent chloroform was removed under reduced pressure, and column chromatography of the residue gave 0.206g of the objective compound 2d in 62% yield.
Example 9
6-methyl-o-azidoaniline 1e (1mmol), α -bromo-tert-butyl ketone (1.2mmol) and potassium carbonate (1.5mmol) were added to a 50mL flask and reacted at 45 ℃ in chloroform (20mL) as a reaction solvent, diphenyl methylphosphine (1.5mmol) was added after 2 hours of reaction, reaction was continued at 30 ℃ for 3 hours, chloroform was removed under reduced pressure as a solvent, the residue was transferred to a chloroform (15mL) solution containing triphenylphosphine (2.5mmol) and iodine as a simple substance (2.5mmol), imidazole acetic acid (1.5mmol) was added and reacted at 45 ℃ for 2 hours, and after completion of reaction, chloroform was removed under reduced pressure as a solvent, and column chromatography of the residue gave 0.146g of the objective compound 2e in 47% yield.
Example 10
Bactericidal activity test (with toxic medium)
The liquid medicine concentration is 200ppm, strain agar sheet is taken by a 5mm puncher, the hypha face downwards is inoculated on a PDA culture medium containing the drug to be detected, the PDA culture medium is placed in the center of a circular culture medium, and the strain agar sheet is cut without sliding so as to avoid polluting the culture medium. Three samples to be detected are inoculated, a culture medium which does not contain a medicine and contains DMSO with the same concentration is used as an air-white illumination, the samples are placed in a biochemical incubator to be cultured for 3-5 days at 25 ℃, and then the diameters of colonies on the culture medium are measured. And (3) observing the influence of the sample to be detected on the growth of hyphae by comparing with the blank control group, and calculating the inhibition rate of the sample to be detected on the growth of colonies under 200 mg/L. Inhibition (%) × (blank colony diameter-diameter of sample colony to be tested)/(blank colony diameter-diameter of punch) ] × 100%. Table 1 shows the results of measurement of a part of Compound (I).
Table 1: results of bacteriostatic Activity test of Compound (I)
As can be seen from table 1 above, the compounds represented by formula (I) of the present invention have certain inhibitory activities against rhizoctonia solani (rhizoctonia solani), Gibberella zeae (Gibberella saubinetii) and Penicillium italicum (Penicillium italicum). Among them, compound 4 is most effective.
The above-described embodiments are merely preferred embodiments of the present invention, and should not be construed as limiting the present invention, and features in the embodiments and examples in the present application may be arbitrarily combined with each other without conflict. The protection scope of the present invention is defined by the claims, and includes equivalents of technical features of the claims. I.e., equivalent alterations and modifications within the scope hereof, are also intended to be within the scope of the invention.
Claims (8)
1. A tert-butyl-containing N-imidazole acetyl dihydroquinoxaline derivative is characterized by having a structure expressed by a general formula (I):
wherein R in the formula is hydrogen, fluorine, chlorine, trifluoromethyl or methyl; the position and the number of the substituent groups are not fixed.
2. The tert-butyl-containing N-imidazoleacetyl dihydroquinoxaline derivative according to claim 1, wherein R is fluorine, two in number and meta, and has a structural formula:
3. the process for producing a tert-butyl group-containing N-imidazoleacetyldihydroquinoxaline derivative according to claim 1,
(1) sequentially adding an o-azidoaniline derivative, an alpha-bromo-tert-butyl ketone derivative and potassium carbonate into a container filled with an organic solvent, reacting at 40-50 ℃ for 2-8 hours, adding diphenyl methyl phosphine, and reacting at 25-32 ℃ for 2-6 hours;
(2) after the reaction in the step (1) is finished, removing the organic solvent under reduced pressure, transferring the residue to a chloroform solution containing triphenylphosphine and iodine simple substances, adding imidazole acetic acid, reacting at 40-50 ℃ for 1-5 hours, after the reaction is finished, removing the organic solvent under reduced pressure, and performing column chromatography on the residue to obtain a compound 2 containing the N-imidazole acetyl dihydroquinoxaline derivative of the tert-butyl group;
the synthesis route is as follows:
4. the process for producing a t-butyl-containing N-imidazoleacetyldihydroquinoxaline derivative according to claim 3, wherein in the step (1), the molar ratio of the o-azidoaniline derivative, the α -bromo-t-butylketone derivative, the potassium carbonate, and the diphenylmethylphosphine is 1: 0.1-3: 0.1-3: 0.1-3.
5. The process for producing a tert-butyl group-containing N-imidazoleacetyldihydroquinoxaline derivative according to claim 3, wherein the molar ratio of triphenylphosphine, iodine, imidazole acetic acid and the o-azidoaniline derivative in the step (1) in the step (2) is 0.1 to 6: 0.1-6: 0.1-3: 1.
6. the method for preparing N-imidazoleacetyldihydroquinoxaline derivatives having a tert-butyl group according to claim 3, wherein the o-azidoaniline derivative is any one of o-azidoaniline, 4-chloro-o-azidoaniline, 4-methyl-o-azidoaniline, 6-methyl-o-azidoaniline, and 4, 6-dimethyl-o-azidoaniline.
7. The process for producing a tert-butyl-containing N-imidazoleacetyldihydroquinoxaline derivative according to claim 3, wherein the organic solvent used in the steps (1) and (2) is chloroform.
8. The use of the t-butyl-containing N-imidazoleacetyldihydroquinoxaline derivatives according to claim 1 for the preparation of a medicament for inhibiting Rhizoctonia solani, Gibberella tritici and Penicillium italicum.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811361161.8A CN109265448B (en) | 2018-11-15 | 2018-11-15 | Tert-butyl-containing N-imidazole acetyl dihydroquinoxaline derivative, synthesis method and application thereof as bactericide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811361161.8A CN109265448B (en) | 2018-11-15 | 2018-11-15 | Tert-butyl-containing N-imidazole acetyl dihydroquinoxaline derivative, synthesis method and application thereof as bactericide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109265448A CN109265448A (en) | 2019-01-25 |
| CN109265448B true CN109265448B (en) | 2020-09-15 |
Family
ID=65189363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811361161.8A Active CN109265448B (en) | 2018-11-15 | 2018-11-15 | Tert-butyl-containing N-imidazole acetyl dihydroquinoxaline derivative, synthesis method and application thereof as bactericide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109265448B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104829598A (en) * | 2015-05-27 | 2015-08-12 | 贵州大学 | Quinazolinone compound containing 1, 2, 4-triazole thioether and synthesizing method and application of quinazolinone compound |
| CN105524047A (en) * | 2015-12-27 | 2016-04-27 | 贵州大学 | Synthetic method and application of quinazolinone compounds containing 1,2,4-triazolethione Schiff base |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7439241B2 (en) * | 2003-05-27 | 2008-10-21 | Galderma Laboratories, Inc. | Compounds, formulations, and methods for treating or preventing rosacea |
-
2018
- 2018-11-15 CN CN201811361161.8A patent/CN109265448B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104829598A (en) * | 2015-05-27 | 2015-08-12 | 贵州大学 | Quinazolinone compound containing 1, 2, 4-triazole thioether and synthesizing method and application of quinazolinone compound |
| CN105524047A (en) * | 2015-12-27 | 2016-04-27 | 贵州大学 | Synthetic method and application of quinazolinone compounds containing 1,2,4-triazolethione Schiff base |
Non-Patent Citations (1)
| Title |
|---|
| 喹噁啉-1，4-N-二氧化物的抗微生物的活性的研究进展;程古月等;《中国新药杂志》;20170210;第26卷(第2期);全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109265448A (en) | 2019-01-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Tirkey et al. | Synthesis, characterization and antibacterial studies of ferrocenyl and cymantrenyl hydrazone compounds | |
| CN111533715A (en) | 2(5H) -furan-2-one derivative, preparation method thereof and application thereof in inhibiting rice tillering | |
| CN109265448B (en) | Tert-butyl-containing N-imidazole acetyl dihydroquinoxaline derivative, synthesis method and application thereof as bactericide | |
| US10674723B2 (en) | 1,8-bis(Schiff base)-p-menthane derivatives as well as preparation method and applications thereof | |
| CN109384770B (en) | N-substituted triazole acetyl tert-butyl dihydroquinoxaline derivatives, synthesis method and application thereof as bactericide | |
| CN113563281B (en) | Benzophenone compound containing 1,3, 4-thiadiazole thioether structure and application thereof | |
| CN108059613B (en) | Pyrazole amide compound and application thereof | |
| CN109400589B (en) | Quinoxaline bactericide, preparation method and application thereof | |
| CN110372774B (en) | Isoindolone substituted alpha-acyloxy amide dipeptide derivative and synthesis method thereof | |
| CN109400588B (en) | Fluorine-containing triazole quinoxaline bactericide, preparation method and application thereof | |
| CN103141486B (en) | Application of 4-(benzofuran-5-yl)-2-phenzyl aminothiazole as bactericide | |
| Shcherbakov et al. | Synthesis of N-Alkyl Enamino Ketones Based on 3-Acyl-4 H-polyfluorochromen-4-ones and Their Antimicrobial Activity | |
| CN113387778B (en) | Meta-alkenyl substituted aryl alkyl ether and preparation method and application thereof | |
| Fang et al. | Synthesis and evaluation of novel ferrocene‐substituted triadimenol analogues | |
| CN111285807A (en) | Pyrazole amide compound and application thereof | |
| CN112961185B (en) | Fluorine-containing coumarin phosphate derivative and preparation method and application thereof | |
| CN117964549A (en) | Synthesis and antibacterial application of novel thymol derivative containing piperidine and sulfonamide active fragments | |
| RU2781210C1 (en) | Method for preparation of 1-geranylbenzimidazole | |
| CN113149927B (en) | Vanillin isoxazole compound and preparation method and application thereof | |
| CN109897052B (en) | N-pyrimidinyl-1, 3-oxaza bridge ring compound and preparation method and application thereof | |
| CN114957113B (en) | 2-chloroquinoline-3-formaldehyde oxime-O- (N-p-fluorophenyl) carbamate and preparation method and application thereof | |
| CN111763231B (en) | Synthesis method and application of triphenyl phosphonium cation-containing bactericidal and acaricidal compound | |
| CN105777773A (en) | Thiophene[2,3-b]quinoline derivative and synthetic method and application thereof | |
| RU2584692C2 (en) | Method of producing 3-(1-adamantyl)-1,5,3-ditiazepane and use thereof as fungicidally active agent | |
| JPS6341476A (en) | Novel tricyclic azole derivative, production thereof and agricultural and horticultural fungicide containing said derivative as active ingredient |
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 |