CN112174908B - N- (arylaminoethyl) benzoxazolone compound and preparation method and application thereof - Google Patents
N- (arylaminoethyl) benzoxazolone compound and preparation method and application thereof Download PDFInfo
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- CN112174908B CN112174908B CN202011230896.4A CN202011230896A CN112174908B CN 112174908 B CN112174908 B CN 112174908B CN 202011230896 A CN202011230896 A CN 202011230896A CN 112174908 B CN112174908 B CN 112174908B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
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- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
Abstract
The invention provides an N- (arylaminoethyl) benzoxazolone compound for crop bacteriostasis, a preparation method and application thereof. The compound is prepared by reacting an arylamine compound with N- (2-bromoethyl) benzoxazolone, and the preparation method has the advantages of low cost and easy acquisition of synthetic materials and simple synthetic method. Meanwhile, the compound has good inhibition effect on the activity of crop pathogens, in particular to obvious inhibition effect on the activity of wheat scab pathogens, cucumber botrytis cinerea pathogens, phytophthora capsici, sclerotinia rot pathogens, rice sheath blight pathogens, rice blast pathogens and other pathogens.
Description
Technical Field
The invention relates to a benzoxazolone compound, in particular to an N- (arylaminoethyl) benzoxazolone compound with bactericidal activity, a preparation method thereof and bactericidal application thereof; belongs to the technical field of pesticides.
Background
Among crop infectious diseases, there are mainly two kinds of fungal diseases and bacterial diseases, wherein the fungal diseases account for about 80% of the diseases. The prevention and control methods and the medicament use are also quite different due to the different sources of fungal diseases and bacterial diseases.
Effects of fungal diseases on crops: the plant cell expansion and division can be initiated, the damaged part is formed into root swelling or goiter, downy mildew, saprophytic and weak parasitic bacteria are initiated, the tissue necrosis of flowers, fruits, tubers and other storage organs of the plant is caused, the tissue necrosis of the plant is initiated, wherein the plant cell expansion and division does not have spore pathogenic fungi, the root and the stem basal part are mainly affected, the root rot and the stem basal rot are caused, the dredged tissue of the affected plant is also mainly affected, and the whole plant system morbidity such as fusarium wilt, verticillium wilt and the like is caused. The disease symptoms caused by the various types and kinds of fungal diseases are also becoming variable. However, any fungal disease occurs at any place, and the symptoms are expressed, and hyphae and spores are produced under moist conditions. This is the main basis for judging fungal diseases.
Bacterial diseases are mainly represented by: necrosis and rot, wilting and malformation. Necrosis, decay and malformation are all consequences of bacterial destruction of thin cell wall tissue. On the leaf of the reticulate vein, the disease spots are polygonal spots, and yellow halo is arranged around the disease spots. Lesions on hypertrophic tissues or fruits are mostly circular. On tender, succulent tissue, the tissue dies and is prone to decay. Some parts are damaged and then cause accelerated lesions to form tumors, which often occur in roots or stems. Wilting is the result of a cell infecting the vascular bundle, and may occur locally or entirely. After vascular bundle cells are destroyed, moisture and nutrient substances cannot be normally transported, and plant wilting and death can be caused. The cell diseases have no hypha and spore, the surface of the disease spots has no mould, but the bacterial pus (the bacteria for removing the root cancer) overflows, and the surface of the disease spots is smooth, which is the main basis for diagnosing the bacterial diseases. One of the effective methods for effectively preventing crops from being affected by germs is to inhibit the physiological activity of germs through medicines, further inhibit proliferation and diffusion of crops, compress living space of germs, and further reduce or even eliminate the damage of germs to crops.
Most heterocyclic compounds have a very wide range of biological activities, and among them, heterocyclic compounds containing nitrogen and oxygen are particularly important. The benzoxazolone compounds contain nitrogen and oxygen heteroatoms, are generally regarded as important scaffolds for drug discovery, and show excellent biological activities such as sterilization, disinsection, weeding, anti-tumor, anti-inflammatory and the like. Is widely applied to the fields of medicines and agrochemicals, and has good research value and application prospect. Thus, the first and second substrates are bonded together,
however, no report on N- (arylaminoethyl) benzoxazolone compounds and application thereof in inhibiting crop strains is reported in the literature. Therefore, we synthesize a class of N- (arylaminoethyl) benzoxazolone compounds, and research the inhibitory activity of the compounds on wheat scab, cucumber gray mold, phytophthora capsici, sclerotinia rot, rice sheath blight or rice blast.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides an N- (arylaminoethyl) benzoxazolone compound for crop bacteriostasis and a preparation method thereof. The compound has the advantages of simple preparation method, readily available raw materials, good antibacterial and bactericidal activity on crop pathogens, and particularly obvious inhibition effect on the activities of wheat scab pathogen, cucumber gray mold pathogen, phytophthora capsici, sclerotinia rot pathogen, rice sheath blight pathogen or rice blast pathogen and other pathogens, and the yield of crops is well ensured.
According to a first embodiment of the present invention, there is provided an N- (arylaminoethyl) benzoxazolone compound.
An N- (arylaminoethyl) benzoxazolone compound which is a compound with a structural general formula (I),
in the formula (I), R is hydrogen or C 1 -C 2 Alkyl or C 1 -C 2 Alkoxy or halogen.
Preferably, R is hydrogen, methyl, methoxy, dimethyl or halogen.
Preferably, R is H, 4-CH 3 O、3-CH 3 O、2-CH 3 O、4-CH 3 、3-CH 3 、2-CH 3 、4-Cl、3-Cl、3,4-(CH 3 ) 2 4-F or 4-Br.
Preferably, the compound having the general structural formula (I) is any one of the following substances:
n- ((4-toluidinyl) ethyl) benzoxazolone:
n- ((3-methylanilino) ethyl) benzoxazolone:
n- ((2-methylanilino) ethyl) benzoxazolone:
n- ((4-methoxyanilino) ethyl) benzoxazolone:
n- ((3-methoxyanilino) ethyl) benzoxazolone:
n- ((2-methoxyanilino) ethyl) benzoxazolone:
n- ((4-chloroanilino) ethyl) benzoxazolone:
n- ((3-chloroanilino) ethyl) benzoxazolone:
n- ((anilino) ethyl) benzoxazolone:
n- ((3, 4-dimethylanilino) ethyl) benzoxazolone:
n- ((4-fluoroanilino) ethyl) benzoxazolone:
n- ((4-bromoanilino) ethyl) benzoxazolone:
according to a second embodiment of the present invention, there is provided a process for preparing N- (arylaminoethyl) benzoxazolones of the general structural formula (I),
the method comprises the following steps:
1) Reacting an arylamine compound having a general structural formula (II) with N- (2-bromoethyl) benzoxazolone to obtain a mixture containing a compound having a general structural formula (I):
2) Separating and purifying the mixture containing the compound with the structural general formula (I) obtained in the step 1) to obtain the N- (arylaminoethyl) benzoxazolone compound with the structural general formula (I);
in the formulae (I) and (II), R is hydrogen or C 1 -C 2 Alkyl or C 1 -C 2 Alkoxy or halogen.
Preferably, in formulae (I) and (II), R is hydrogen, methyl, methoxy, dimethyl or halogen.
Preferably, in formulae (I) and (II), R is H, 4-CH 3 O、3-CH 3 O、2-CH 3 O、4-CH 3 、3-CH 3 、2-CH 3 、4-Cl、3-Cl、3,4-(CH 3 ) 2 4-F or 4-Br.
Preferably, step 1) is carried out in an organic solvent to which a catalyst and a base are also added.
Preferably, the catalyst is sodium iodide, potassium iodide or sodium bromide, preferably sodium iodide.
Preferably, the base is potassium carbonate, sodium hydroxide or potassium hydroxide, preferably potassium carbonate.
Preferably, the organic solvent is chloroform, dimethylsulfoxide or acetonitrile, preferably acetonitrile.
In the present invention, in step 1): the molar ratio of the arylamine compound with the structural formula (II) to the N- (2-bromoethyl) benzoxazolone is 1.0-1.4:1, preferably 1.05-1.3:1, more preferably 1.1-1.2:1.
In the invention, the step 1) specifically comprises the following steps: firstly adding a compound N- (2-bromoethyl) benzoxazolone and a catalyst into a reaction vessel, then adding a solvent into the reaction vessel, carrying out reflux reaction, and cooling to room temperature; then adding arylamine compounds with the structural general formula (II) and alkali for reaction to obtain a mixture containing the compounds with the structural general formula (I).
Preferably, the temperature of the reflux reaction is from 80 ℃ to 110 ℃, preferably from 90 ℃ to 100 ℃, for example 92 ℃,95 ℃,98 ℃.
Preferably, the reflux reaction is carried out for a period of 15 to 60 minutes, preferably 20 to 45 minutes, for example 25 minutes, 30 minutes, 35 minutes, 40 minutes.
Preferably, the reaction of the arylamine compound of formula (II) with a base is carried out at a temperature of 80℃to 110℃and preferably 90℃to 100℃such as 92℃and 95℃and 98 ℃.
Preferably, the reaction time of the arylamine compound having the general structural formula (II) with the base is 12 to 72 hours, preferably 24 to 48 hours, for example 22 hours, 25 hours, 28 hours, 30 hours, 32 hours, 35 hours, 38 hours, 40 hours, 42 hours, 45 hours.
In the invention, the step 2) is specifically: separating (preferably filtering or suction filtering) the mixture obtained in step 1) and containing the compound of formula (I), subjecting the filtrate to column chromatography to obtain the product after reduced pressure desolventizing, and drying (using anhydrous MgSO) 4 Or Na (or) 2 SO 4 Drying) to obtain the N- (arylaminoethyl) benzoxazolone compound with the structural general formula (I).
According to a third embodiment of the present invention, there is provided the use of an N- (arylaminoethyl) benzoxazolone compound.
Use of an N- (arylaminoethyl) benzoxazolone compound having the structural formula (I) according to the first embodiment or an N- (arylaminoethyl) benzoxazolone compound having the structural formula (I) prepared according to the method of the second embodiment for inhibiting gibberella zeae, botrytis cinerea, phytophthora capsici, sclerotinia sclerotiorum, rhizoctonia solani or Pyricularia oryzae.
Or the N- (arylaminoethyl) benzoxazolone compound with the structural formula (I) in the first embodiment or the N- (arylaminoethyl) benzoxazolone compound with the structural formula (I) prepared by the method in the second embodiment is used for preparing the medicine for inhibiting the fusarium graminearum, the cucumber gray mold germ, the phytophthora capsici, the sclerotium germ, the sheath blight germ or the rice blast germ.
In the present invention, an arylamine compound having the general formula (II) and N- (2-bromoethyl) benzoxazolone are reacted in the presence of a catalyst, a base, and an organic solvent by a one-pot method to obtain a reaction mixture containing the compound having the general formula (I). The preparation method provided by the invention is simple, high in yield and easy to separate and purify.
In the present invention, N- (2-bromoethyl) benzoxazolone is prepared by the following method: the benzoxazolinone and 1, 2-dibromoethane are reacted in an organic solvent with a catalyst to obtain the N- (2-bromoethyl) benzoxazolinone.
The method comprises the following steps: weighing benzoxazolinone and cesium carbonate, adding the benzoxazolinone and cesium carbonate into a reaction vessel, adding tetrabutylammonium iodide and 1, 2-dibromoethane, heating for reaction, cooling to room temperature, filtering out solids, decompressing and desolventizing filtrate, and separating by column chromatography.
In this reaction, benzoxazolinone, cesium carbonate, tetrabutylammonium iodide and 1, 2-dibromoethane are added in a molar ratio of 1:1 to 20:0.1 to 1:0.5 to 20, preferably 1:1.2 to 10:0.15 to 0.8:1 to 15, more preferably 1:1.5 to 5:0.2 to 0.6:1 to 10.
The temperature of the reaction is 45-100deg.C, preferably 50-80deg.C, more preferably 55-70deg.C. The reaction time of the reaction is 2 to 24 hours, preferably 6 to 18 hours, more preferably 8 to 15 hours.
The chemical reagent sources or structural formulas used in the invention are as follows:
compared with the prior art, the invention has the following beneficial technical effects:
1. the N- (arylaminoethyl) benzoxazolone compound with the structural general formula (I) is a brand new compound, and has very good antibacterial activity; particularly has remarkable effect of inhibiting the activity of the germs of wheat gibberella, cucumber botrytis, phytophthora capsici, sclerotinia rot, sheath blight of rice or rice blast.
2. The preparation method of the N- (arylaminoethyl) benzoxazolone compound with the structural general formula (I) provided by the invention has the advantages of low cost and easiness in obtaining synthetic materials, simple synthetic method, high yield and easiness in separation and purification.
Drawings
FIG. 1 is a diagram showing the synthetic route of N- (arylaminoethyl) benzoxazolones with the general structural formula (I) according to the invention.
FIG. 2 is a synthetic scheme for preparing the N- (arylaminoethyl) benzoxazolone compounds with the structural general formula (I) in the presence of a catalyst and a base.
Detailed Description
The following examples illustrate the technical aspects of the invention, and the scope of the invention claimed includes but is not limited to the following examples.
The invention provides an N- (arylaminoethyl) benzoxazolone compound.
An N- (arylaminoethyl) benzoxazolone compound which is a compound with a structural general formula (I),
in the formula (I), R is hydrogen or C 1 -C 2 Alkyl or C 1 -C 2 Alkoxy or halogen.
Preferably, R is hydrogen, methyl, methoxy, dimethyl or halogen.
Preferably, R is H, 4-CH 3 O、3-CH 3 O、2-CH 3 O、4-CH 3 、3-CH 3 、2-CH 3 、4-Cl、3-Cl、3,4-(CH 3 ) 2 4-F or 4-Br.
Preparation example 1
Preparation of N- (2-bromoethyl) benzoxazolone:
0.675g (5 mmol) of benzoxazolinone and 3.26g (10 mmol) of cesium carbonate are weighed into a 100mL single-neck round bottom flask, 0.37g (1 mmol) of tetrabutylammonium iodide and 30mL of 1, 2-dibromoethane are added, the mixture is stirred for 12 hours at the temperature of 65 ℃, the mixture is cooled to room temperature after the reaction, the solid is filtered, the filtrate is decompressed and desolventized, and then the white solid N- (2-bromoethyl) benzoxazolinone is obtained through column chromatography separation.
Example 1: synthesis of N- ((4-toluidinyl) ethyl) benzoxazolone.
The compound N- (2-bromoethyl) benzoxazolone 0.726g (3 mmol) and sodium iodide 0.49g (3.3 mmol) were weighed into a 100ml three-necked flask, 40ml of acetonitrile was further added as a solvent, refluxed for 20 minutes and cooled to room temperature, and then p-toluidine 0.35g (3.3 mmol) and anhydrous potassium carbonate 0.83g (6 mmol) were added. The resulting mixture was stirred at 90℃for 24h (TLC plate tracking), and after completion of the reaction was cooled to room temperature. The precipitate is filtered off, the filtrate is decompressed and desolventized, and then the white solid is obtained through column chromatography, the melting point (mp) is 121.1-123.0 ℃, and the yield is 54%.
1 H NMR(500MHz,Chloroform-d)δ7.19(d,J＝7.7Hz,1H),7.16–7.07(m,2H),7.00(d,J＝8.0Hz,2H),6.89(d,J＝7.4Hz,1H),6.55(d,J＝8.0Hz,2H),4.04(t,J＝6.0Hz,2H),3.55(t,J＝6.1Hz,2H),2.25(s,3H).
13 C NMR(126MHz,Chloroform-d)δ154.95,144.69,142.67,131.31,129.95(2C),127.31,123.93,122.54,112.99(2C),110.11,108.38,42.44,41.63,20.42.
Example 2: synthesis of N- ((3-methylanilino) ethyl) benzoxazolone.
According to the process conditions of example 1, N- (2-bromoethyl) benzoxazolone 0.726g (3 mmol), sodium iodide 0.490g (3.3 mmol), 3-methylaniline 0.354g (3.3 mmol) and anhydrous potassium carbonate 0.828g (6 mmol) were used in 50% yield as white solid. The melting point is 134.0-136.2 ℃.
1 H NMR(500MHz,Chloroform-d)δ7.22–7.16(m,1H),7.19–7.03(m,4H),6.90(d,J＝7.6Hz,1H),6.57(d,J＝7.5Hz,1H),6.43(d,J＝2.3Hz,2H),4.04(t,J＝6.0Hz,2H),3.57(t,J＝6.0Hz,2H),2.28(s,3H).
13 C NMR(126MHz,Chloroform-d)δ155.00,147.17,142.69,139.23,131.30,129.32,123.94,122.57,118.95,113.64,110.11,109.93,108.41,42.12,41.68,21.65.
Example 3: synthesis of N- ((2-methylanilino) ethyl) benzoxazolone.
According to the process conditions of example 1, N- (2-bromoethyl) benzoxazolone 0.726g (3 mmol), sodium iodide 0.490g (3.3 mmol), 2-methylaniline 0.354g (3.3 mmol) and anhydrous potassium carbonate 0.828g (6 mmol) were used in 47% yield as white solid. The melting point is 115.2-118.4 ℃.
1 HNMR(500MHz,Chloroform-d)δ7.11(m,4H),7.02(d,J＝7.3Hz,1H),6.80(d,J＝6.8Hz,1H),6.67(t,J＝7.3Hz,1H),6.61(d,J＝8.0Hz,1H),4.07(t,J＝5.7Hz,2H),3.58(t,J＝5.7Hz,2H),1.99(s,3H).
13 C NMR(126MHz,Chloroform-d)δ155.19,145.06,142.68,131.27,130.45,127.17,123.95,122.61,122.53,117.59,110.15,109.16,108.19,42.17,41.40,17.43.
Example 4: synthesis of N- ((4-methoxyanilino) ethyl) benzoxazolone.
According to the process conditions of example 1, N- (2-bromoethyl) benzoxazolone 0.726g (3 mmol), sodium iodide 0.490g (3.3 mmol), p-methoxyaniline 0.406g (3.3 mmol) and anhydrous potassium carbonate 0.828g (6 mmol) were obtained in 58% yield as a white solid. The melting point is 134.0-136.2 ℃. .
1 H NMR(500MHz,Chloroform-d)δ7.17(d,J＝7.9Hz,1H),7.10(dd,J＝12.9,7.5Hz,2H),6.87(d,J＝7.5Hz,1H),6.77(d,J＝8.7Hz,2H),6.57(d,J＝8.5Hz,2H),4.02(t,J＝6.0Hz,2H),3.73(s,3H),3.52(t,J＝6.0Hz,2H).
13 C NMR(126MHz,Chloroform-d)δ154.92,152.57,142.67,140.99,131.28,123.90,122.54,115.05(2C),114.24(2C),110.11,108.34,55.80,42.99,41.65.
Example 5: synthesis of N- ((3-methoxyanilino) ethyl) benzoxazolone.
According to the process conditions of example 1, N- (2-bromoethyl) benzoxazolone 0.726g (3 mmol), sodium iodide 0.490g (3.3 mmol), 3-methoxyaniline 0.406g (3.3 mmol) and anhydrous potassium carbonate 0.828g (6 mmol) were prepared in 52% yield as a yellow solid. Melting point 132.2-135.7 ℃.
1 H NMR(500MHz,Chloroform-d)δ7.18(d,J＝7.6Hz,1H),7.15–7.01(m,3H),6.87(d,J＝7.5,1H),6.29(dd,J＝8.2,2.5Hz,1H),6.25–6.18(m,1H),6.15(t,J＝2.2Hz,1H),4.03(t,J＝6.0Hz,2H),3.74(s,3H),3.54(t,J＝6.0Hz,2H).
13 C NMR(126MHz,Chloroform-d)δ160.95,154.98,148.48,142.68,131.27,130.23,123.94,122.58,110.15,108.32,105.77,103.25,98.74,55.14,42.13,41.54.
Example 6: synthesis of N- ((2-methoxyanilino) ethyl) benzoxazolone.
According to the process conditions of example 1, N- (2-bromoethyl) benzoxazolone 0.726g (3 mmol), sodium iodide 0.490g (3.3 mmol), 2-methoxyaniline 0.406g (3.3 mmol) and anhydrous potassium carbonate 0.828g (6 mmol) were prepared in 48% yield as a white solid. Melting point 108.5-111.2 deg.c.
1 HNMR(500MHz,Chloroform-d)δ7.12(d,J＝7.0Hz,1H),7.09–6.98(m,2H),6.85(t,J＝7.0Hz,1H),6.78(d,J＝8.9Hz,1H),6.71(d,J＝6.8Hz,1H),6.66(m,2H),4.49(s,1H),3.98(t,J＝6.2Hz,2H),3.69(s,3H),3.55(t,J＝6.2Hz,2H).
13 C NMR(126MHz,Chloroform-d)δ154.75,147.03,142.67,137.10,131.40,123.79,122.41,121.33,117.24,109.98,109.94,109.62,108.34,55.46,41.60,41.46.
Example 7: synthesis of N- ((4-chloroanilino) ethyl) benzoxazolone.
According to the process conditions of example 1, N- (2-bromoethyl) benzoxazolone 0.726g (3 mmol), sodium iodide 0.490g (3.3 mmol), parachloroaniline 0.421g (3.3 mmol) and anhydrous potassium carbonate 0.828g (6 mmol) in 50% yield as white solid. Melting point 146.2-149.8deg.C
1 H NMR(500MHz,Chloroform-d)δ7.18–7.06(m,5H),6.86(d,J＝7.5Hz,1H),6.50(d,J＝8.5Hz,2H),4.01(t,J＝5.9Hz,2H),3.52(t,J＝5.9Hz,2H).
13 C NMR(126MHz,Chloroform-d)δ155.01,145.71,142.63,131.12,129.23(2C),124.01,122.69,122.45,113.82(2C),110.19,108.23,42.17,41.43.
Example 8: synthesis of N- ((3-chloroanilino) ethyl) benzoxazolone.
According to the process conditions of example 1, N- (2-bromoethyl) benzoxazolone 0.726g (3 mmol), sodium iodide 0.490g (3.3 mmol), 3-chloroaniline 0.421g (3.3 mmol) and anhydrous potassium carbonate 0.828g (6 mmol) were used in 42% yield as white solid. Melting point 124.2-126.8 deg.C.
1H NMR(500MHz,Chloroform-d)δ7.20(d,J＝7.7Hz,1H),7.14(m,2H),7.07(t,J＝8.0Hz,1H),6.88(d,J＝7.4Hz,1H),6.68(d,J＝7.7Hz,1H),6.56(s,1H),6.47(d,J＝8.3Hz,1H),4.15(s,1H),4.05(t,J＝5.9Hz,2H),3.55(t,J＝5.8Hz,2H).
13C NMR(126MHz,Chloroform-d)δ155.04,148.25,142.69,135.18,131.09,130.41,124.01,122.73,117.88,112.29,111.15,110.28,108.14,42.05,41.44.
Example 9: synthesis of N- ((anilino) ethyl) benzoxazolone.
According to the process conditions of example 1, N- (2-bromoethyl) benzoxazolone 0.726g (3 mmol), sodium iodide 0.490g (3.3 mmol), aniline 0.307g (3.3 mmol) and potassium carbonate 0.828g (6 mmol) in 52% yield as a white solid. Melting point 118.0-121.3 deg.c.
1H NMR(500MHz,Chloroform-d)δ7.17–6.96(m,5H),6.82(d,J＝7.7Hz,1H),6.68(t,J＝7.3Hz,1H),6.56(d,J＝8.0Hz,2H),3.95(t,J＝6.1Hz,2H),3.48(t,J＝6.1Hz,2H).
13C NMR(126MHz,Chloroform-d)δ154.98,147.24,142.64,131.32,129.47(2C),123.99,122.56,117.91,112.81(2C),110.06,108.49,42.00,41.55.
Example 10:
synthesis of N- ((3, 4-dimethylanilino) ethyl) benzoxazolone according to the procedure of example 1.
0.726g (3 mmol) of N- (2-bromoethyl) benzoxazolone, 0.490g (3.3 mmol) of sodium iodide, 0.400g (3.3 mmol) of 3, 4-dimethylaniline and 0.828g (6 mmol) of anhydrous potassium carbonate, yield 56% of white solid. Melting point 105.1-108.7 deg.c.
1 H NMR(500MHz,Chloroform-d)δ7.18-7.13(m,1H),7.13–7.03(m,2H),6.91(d,J＝8.1Hz,1H),6.87(d,J＝7.6,1H),6.40(s,1H),6.36(dd,J＝8.0,2.6Hz,1H),3.99(t,J＝6.0Hz,2H),3.92–3.67(m,1H),3.50(t,J＝6.0Hz,2H),2.16(s,3H),2.13(s,3H).
13 C NMR(126MHz,Chloroform-d)δ154.96,145.26,142.69,137.52,131.35,130.46,125.99,123.91,122.52,114.75,110.21,110.08,108.45,42.43,41.77,20.08,18.75.
Example 11: synthesis of N- ((4-fluoroanilino) ethyl) benzoxazolone.
According to the process conditions of example 1, N- (2-bromoethyl) benzoxazolone 0.726g (3 mmol), sodium iodide 0.490g (3.3 mmol), 4-fluoroaniline 0.367g (3.3 mmol) and anhydrous potassium carbonate 0.828g (6 mmol) were used in 45% yield as a white solid.
1 H NMR(500MHz,Chloroform-d)δ7.18(d,J＝7.7Hz,1H),7.12(dq,J＝15.3,7.6Hz,2H),6.92–6.85(m,3H),6.53(dd,J＝8.8,4.2Hz,2H),4.04(t,J＝5.9Hz,2H),3.53(t,J＝5.9Hz,2H).
13 C NMR(126MHz,Chloroform-d)δ154.86,152.81,141.13,140.50,129.00,121.77,120.47,113.78,113.60,111.52,111.46,108.03,106.02,40.53,39.37.
Example 12: synthesis of N- ((4-bromoanilino) ethyl) benzoxazolone.
According to the process conditions of example 1, N- (2-bromoethyl) benzoxazolone 0.726g (3 mmol), sodium iodide 0.490g (3.3 mmol), 4-bromoaniline 0.567g (3.3 mmol) and anhydrous potassium carbonate 0.828g (6 mmol) were prepared in 40% yield as a white solid.
1 H NMR(500MHz,Chloroform-d)δ7.23(d,J＝8.4Hz,2H),7.18(d,J＝7.8Hz,1H),7.16–7.07(m,2H),6.86(d,J＝7.4Hz,1H),6.47(d,J＝8.6Hz,2H),4.02(t,J＝5.8Hz,2H),3.53(t,J＝5.9Hz,2H).
13 C NMR(126MHz,Chloroform-d)δ154.99,145.99,142.66,132.12(2C),131.11,124.00,122.70,114.35(2C),110.24,109.69,108.15,42.19,41.38.
Activity experiments
The bactericidal activity was tested on N- ((4-toluidinyl) ethyl) benzoxazolone, N- ((3-methylanilino) ethyl) benzoxazolone, N- ((2-methylanilino) ethyl) benzoxazolone, N- ((4-methoxyanilino) ethyl) benzoxazolone, N- ((3-methoxyanilino) ethyl) benzoxazolone, N- ((2-methoxyanilino) ethyl) benzoxazolone, N- ((4-chloroanilino) ethyl) benzoxazolone, N- ((3-chloroanilino) ethyl) benzoxazolone, N- ((anilino) ethyl) benzoxazolone, N- ((3, 4-dimethylanilino) ethyl) benzoxazolone, N- ((4-fluoroanilino) ethyl) benzoxazolone and N- ((4-bromoanilino) ethyl) benzoxazolone using an ex vivo method.
The test materials for testing the bactericidal activity are selected from the group consisting of gibberella wheat germ, botrytis cinerea, phytophthora capsici, sclerotinia rot of colza, rhizoctonia solani and Magnaporthe grisea, the test reagents are dissolved in acetone, and then 200g/mL of sorrel-144 emulsifier is used for diluting into 500g/mL of liquid medicine.
Under aseptic operating conditions, 1mL of the compound solution was pipetted into a sterilized dish, and then 9mL of sterilized PDA culture-based dish was pipetted into the dish, and mixed well to prepare a drug-containing plate of the corresponding concentration. And (3) cutting bacterial cakes from the edges of bacterial colonies by using a sterilization puncher with the diameter of 4mm under the aseptic condition, inoculating the bacterial cakes to the center of a medicine-containing flat plate by using an inoculator after the culture medium is solidified, and culturing in an incubator with proper temperature.
Blank control was made with no drug added.
The individual treatments were incubated in an incubator at 24.+ -. 1 ℃ and after 72 hours the colony diameters were observed and measured, and the diameters were measured vertically once for each colony by the crisscross method, and the average value was obtained.
Growth inhibition (%) = (control colony diameter-treated colony diameter) ×100/(control colony diameter-4 mm).
The drug concentration was 50. Mu.g/mL. The bactericidal activity test results are shown in Table I.
Table 1 bactericidal Activity of N- (Arylaminoethyl) benzoxazolones (inhibition/%)
From the above table, the target compounds have good inhibitory activity against the test pathogens. Wherein, the inhibition rate of the compound N- ((4-toluidinyl) ethyl) benzoxazolone to sclerotinia sclerotiorum is 70.7 percent; the inhibition rate of N- ((3-methoxyanilino) ethyl) benzoxazolone to sclerotinia sclerotiorum is 90.9 percent, and the inhibition rate to cucumber botrytis cinerea is 78.6 percent; the inhibition rate of N- ((2-methoxyanilino) ethyl) benzoxazolone to Rhizoctonia solani is 75.6%; the inhibition rate of N- ((3-chloroanilino) ethyl) benzoxazolone to sclerotinia sclerotiorum is 95.2 percent, and the inhibition rate to cucumber botrytis cinerea is 75.7 percent; the inhibition rate of N- ((anilino) ethyl) benzoxazolone to Sclerotinia sclerotiorum is 90.9%; the inhibition rate of N- ((3, 4-dimethylanilino) ethyl) benzoxazolone to sclerotinia sclerotiorum is 75.6 percent, and the inhibition rate to cucumber botrytis cinerea is 72.9 percent; the inhibition rate of N- ((4-bromoanilino) ethyl) benzoxazolone on Sclerotinia sclerotiorum is 73.9%.
Claims (12)
1. An N- (arylaminoethyl) benzoxazolone compound, characterized in that: the N- (arylaminoethyl) benzoxazolone compound is a compound with a structural general formula (I),
in the formula (I), R is hydrogen or dimethyl or C 1 -C 2 An alkoxy group.
2. A compound according to claim 1, characterized in that: r is hydrogen, methoxy or dimethyl.
3. A compound according to claim 1, characterized in that: the compound with the structural general formula (I) is any one of the following substances:
n- ((4-methoxyanilino) ethyl) benzoxazolone:
n- ((3-methoxyanilino) ethyl) benzoxazolone:
n- ((2-methoxyanilino) ethyl) benzoxazolone:
n- ((anilino) ethyl) benzoxazolone:
n- ((3, 4-dimethylanilino) ethyl) benzoxazolone:
4. a method for preparing N- (arylaminoethyl) benzoxazolone compounds with a structural general formula (I),
the method comprises the following steps:
1) Firstly, adding a compound N- (2-bromoethyl) benzoxazolone and a catalyst into a reaction vessel, then adding an organic solvent into the reaction vessel, and adding alkali; reflux reaction, cooling to room temperature; then adding arylamine compounds with the structural general formula (II) and alkali for reaction to obtain a mixture containing the compounds with the structural general formula (I); wherein: the catalyst is sodium iodide, potassium iodide or sodium bromide, the alkali is potassium carbonate, sodium hydroxide or potassium hydroxide, and the organic solvent is chloroform, dimethyl sulfoxide or acetonitrile; the molar ratio of the arylamine compound with the structural general formula (II) to the N- (2-bromoethyl) benzoxazolone is 1.0-1.4:1, a step of; the temperature of the reflux reaction is 80-110 ℃; the reflux reaction time is 15-60min; the reaction temperature of the arylamine compound with the structural general formula (II) and alkali is 80-110 ℃; the reaction time is 12-72h
2) Separating the mixture containing the compound with the structural general formula (I) obtained in the step 1), decompressing and desolventizing filtrate, obtaining a product through column chromatography, and drying to obtain the N- (arylaminoethyl) benzoxazolone compound with the structural general formula (I);
in the formulas (I) and (II), R is hydrogen or dimethyl C 1 -C 2 An alkoxy group.
5. The method according to claim 4, wherein: r is hydrogen, methoxy or dimethyl.
6. The method according to claim 5, wherein: r is H, 4-CH 3 O、3-CH 3 O、2-CH 3 O、3,4-(CH 3 ) 2 。
7. The method according to claim 4, wherein: the catalyst is sodium iodide; the alkali is potassium carbonate; the organic solvent is acetonitrile.
8. The method according to claim 4, wherein: in step 1): the molar ratio of the arylamine compound with the structural general formula (II) to the N- (2-bromoethyl) benzoxazolone is 1.05-1.3:1.
9. the method according to claim 8, wherein: in step 1): the molar ratio of the arylamine compound with the structural general formula (II) to the N- (2-bromoethyl) benzoxazolone is 1.1-1.2:1.
10. the method according to claim 4, wherein: the temperature of the reflux reaction is 90-100 ℃; the reflux reaction time is 20-45min; the reaction temperature of the arylamine compound with the structural general formula (II) and alkali is 90-100 ℃; the reaction time is 24-48h.
11. The method according to claim 4, wherein: the separation adopts filtration or suction filtration, and the drying treatment adopts anhydrous MgSO 4 Or Na (or) 2 SO 4 Drying is performed.
12. Use of an N- (arylaminoethyl) benzoxazolone compound of general structural formula (I) according to any one of claims 1-3, characterized in that: the N- (arylaminoethyl) benzoxazolone compound with the structural general formula (I) is used for preparing medicines for inhibiting gibberella wheat, botrytis cinerea, phytophthora capsici, sclerotinia rot, banded sclerotial blight or rice blast.
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| CN111303065A (en) * | 2020-04-13 | 2020-06-19 | 湖南科技大学 | N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound and preparation method and application thereof |
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| CN111303065A (en) * | 2020-04-13 | 2020-06-19 | 湖南科技大学 | N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound and preparation method and application thereof |
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