CN111303065B - N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound and preparation method and application thereof - Google Patents
N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides an N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound for crop bacteriostasis and a preparation method and application thereof. The compound is prepared by reacting N- (2-chloroethyl) -3, 1-benzoxazine-2-ketone and substituted aniline in the presence of a phase transfer catalyst and alkali. Meanwhile, the compound has good inhibition effect on the activity of crop germs, and particularly has obvious inhibition effect on the activity of wheat scab, cucumber gray mold, phytophthora capsici, sclerotinia sclerotiorum, rice sheath blight or rice blast germs and other germs.
Description
Technical Field
The invention relates to a crop bacteriostatic compound, in particular to an N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound and a preparation method and application thereof, belonging to the technical field of pesticides.
Background
Among the crop infectious diseases, there are two main fungal diseases and bacterial diseases, wherein the fungal diseases account for about 80% of the diseases. Because the fungal diseases and the bacterial diseases have different origins, the control method and the medicament use are also different.
Effects of fungal diseases on crops: the plant growth regulator can cause the expansion and division of crop cells, root swelling or goiter of damaged parts, downy mildew, saprophytic bacteria and weak parasitic bacteria, tissue necrosis of storage organs such as flowers, fruits, root tubers, tubers and the like of crops and generative tissue necrosis of crops, wherein pathogenic fungi without spores mainly invade roots and stem bases to cause root rot and stem base rot and mainly invade leading tissues of the crops to cause systemic diseases of the whole plant, such as blight, verticillium wilt and the like. The types and kinds of fungal diseases cause disease symptoms to vary widely. However, any fungal disease occurs at any site, and any symptom appears, and hyphae and spores are produced under humid conditions. This is the main basis for judging fungal diseases.
Bacterial diseases are mainly characterized by: necrosis and rot, wilting and deformity. Necrosis, rot and deformity are the result of bacteria breaking down thin cell wall tissues. The disease spots are polygonal spots on the leaves of the reticular veins, and yellow halo is formed around the disease spots. The spots on the hypertrophic tissue or fruit are mostly circular. On soft and tender meat and juicy tissues, the tissues die and are easy to rot. Some parts are damaged and then have accelerated pathological changes to form tumors, which are mostly generated on roots or stems. Wilting is the result of cell invasion of vascular bundles and may occur locally or fully. After vascular bundle cells are damaged, water and nutrient substances cannot be normally conveyed, and plant wilting death can be caused. The cellular diseases have no hypha and spore, the scab surface has no mildew, but the pus (except for root cancer germ) overflows, and the scab surface is smooth, which is the main basis for diagnosing the bacterial diseases. One of the effective methods of effectively preventing crops from being damaged by pathogenic bacteria is to inhibit the physiological activity of pathogenic bacteria through medicaments, further inhibit the proliferation and the diffusion of the crops, compress the living space of the pathogenic bacteria, and further reduce or even eliminate the damage of the pathogenic bacteria to the crops.
The 3, 1-benzoxazinones generally have a wide range of biological activities such as bactericidal, anti-inflammatory, inhibition of human proteases, anti-cancer, PR antagonists, etc. Therefore, the synthesis and application of the 3, 1-benzoxazinone compounds are receiving wide attention. In 2002, Puwen Zhang and the like synthesize 6-aryl benzoxazinone compounds as PR antagonists, have obvious selectivity advantage compared with mifepristone, can be found to be used as novel contraceptives and used for treating hormone-dependent cancers, non-malignant chronic diseases and the like. In 2005, Antoni Torrens et al synthesized 2-benzoxazinone derivatives as NPYY5 antagonists, with very good binding affinity for NPYY5 receptor, and showed functional antagonism in forskolin-induced cyclic AMP assay. In 2009, Takashi Mizutani et al synthesized novel and highly efficient benzoxazinone derivatives as novel long-chain fatty acid elongase 6(ELOVL 6) inhibitors, which showed effective and selective inhibitory activity against human ELOVL6, as well as double inhibitory activity against mouse ELOVL3 and ELOVL 6. In 2018, benzoxazinone derivatives synthesized by Eman A El-Bordany and the like show high antitumor and cytotoxic activity on human breast cancer cells. In 2019, Ahmed El-Mekabaity and the like synthesized the 3, 1-benzoxazinone derivative which has strong cytotoxicity effect on MCF-7 compared with positive control adriamycin.
However, no report on N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compounds and their use for inhibiting crop strains is found in the literature. Therefore, N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compounds are synthesized, and the inhibitory activity of the compounds on wheat scab, cucumber gray mold, phytophthora capsici, sclerotinia sclerotiorum, rice sheath blight or rice blast is researched.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides an N- (arylamino ethyl) -3, 1-benzoxazine-2-ketone compound for crop bacteriostasis and a preparation method thereof. The compound has simple preparation method and easily obtained raw materials, simultaneously has good bacteriostatic and bactericidal activity on the activity of crop pathogenic bacteria, particularly has obvious activity inhibition effect on wheat scab, cucumber gray mold, phytophthora capsici, sclerotinia sclerotiorum, rice sheath blight or rice blast and other pathogenic bacteria, and well ensures the yield of crops.
In order to achieve the above purpose, the technical scheme provided by the invention is as follows:
according to a first embodiment of the present invention, there is provided an N- (arylaminoethyl) -3, 1-benzoxazine-2-one compound which is a compound having the general structural formula (I):
wherein, in the formula (I), R is hydrogen or C1-C2Alkyl or halogen or C1-C2An alkoxy group.
Preferably, R is selected from one of H, methyl, ethyl, F, Cl, Br, methoxy and ethoxy.
Preferably, R is selected from H, 4-CH3、3-CH3、2-CH3、4-Cl、3-Cl、2-Cl、4-OCH3、3-OCH3、2-OCH3One kind of (1).
Preferably, the N- (arylaminoethyl) -3, 1-benzoxazine-2-one compound is one or more selected from the group consisting of:
n- ((4-methylanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((3-methylanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((2-methylanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((anilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((4-chloroanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((3-chloroanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((2-chloroanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((4-methoxyanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((3-methoxyanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((2-methoxyanilino) ethyl) -3, 1-benzoxazin-2-one:
according to a second embodiment of the present invention there is provided a process for the preparation of the N- (arylaminoethyl) -3, 1-benzoxazin-2-ones of the general structural formula (I) set forth in the first embodiment:
the preparation method comprises the following steps:
1) the reaction of anthranilic alcohol with triphosgene gives 3, 1-benzoxazine-2-one:
2) reacting the 3, 1-benzoxazine-2-one obtained in step 1) with 1, 2-dichloroethane to obtain N- (2-chloroethyl) -3, 1-benzoxazine-2-one having the structural formula (II):
3) reacting the N- (2-chloroethyl) -3, 1-benzoxazine-2-one of formula (II) obtained in step 2) with a substituted aniline of general structural formula (III) to obtain a reaction mixture comprising N- (arylaminoethyl) -3, 1-benzoxazine-2-one compounds of general structural formula (I):
4) separating and purifying the reaction mixture containing the N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound with the structural general formula (I) obtained in the step 3) to obtain the N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound with the structural general formula (I).
Preferably, R is hydrogen or C1-C2Alkyl or halogen or C1-C2An alkoxy group.
Preferably, R is selected from one of H, methyl, ethyl, F, Cl, Br, methoxy and ethoxy.
Preferably, R is selected from H, 4-CH3、3-CH3、2-CH3、4-Cl、3-Cl、2-Cl、4-OCH3、3-OCH3、2-OCH3One kind of (1).
Preferably, in step 1), the anthranilic alcohol is reacted with triphosgene in an organic solvent and in the presence of a base.
Preferably, in step 1), the organic solvent is one of tetrahydrofuran, toluene and 1, 2-dichloroethane. Tetrahydrofuran is preferred.
Preferably, in step 1), the base is triethylamine or pyridine. Triethylamine is preferred.
Preferably, in step 2), the 3, 1-benzoxazine-2-one and 1, 2-dichloroethane are reacted in an organic solvent and in the presence of a base.
Preferably, in step 2), the organic solvent is tetrahydrofuran or toluene. Tetrahydrofuran is preferred.
Preferably, in step 2), the base is cesium carbonate or potassium carbonate. Cesium carbonate is preferred.
Preferably, in step 3), the N- (2-chloroethyl) -3, 1-benzoxazine-2-one and substituted aniline are reacted in an organic solvent in the presence of a base and a phase transfer catalyst.
Preferably, in step 3), the organic solvent is acetonitrile or Dimethylformamide (DMF). Acetonitrile is preferred.
Preferably, in step 3), the base is potassium carbonate or NaOH. Preferably potassium carbonate.
Preferably, in step 3), the phase transfer catalyst is sodium iodide or tetrabutyl ammonium iodide. Sodium iodide is preferred.
Preferably, the anthranilic alcohol, triphosgene, organic solvent and base are added in step 1) in a molar ratio of 1:0.5-1.5:30-120:0.8-3, preferably 1:0.8-1.2:40-100: 1-2.
Preferably, in step 2), the 3, 1-benzoxazine-2-one, 1, 2-dichloroethane, the organic solvent and the base are added in a molar ratio of 1:2-4:20-100:0.5-3, preferably 1:2.5-3.5:30-80: 1-2.5.
Preferably, in step 3), the molar ratio of the N- (2-chloroethyl) -3, 1-benzoxazin-2-one of formula (II) to the amount of substituted aniline of general structural formula (III) added is 1:0.5 to 2, preferably 1:0.8 to 1.8, more preferably 1:1.0 to 1.5.
Preferably, in step 3), the molar ratio of the N- (2-chloroethyl) -3, 1-benzoxazine-2-one, the organic solvent, the base and the phase transfer catalyst is 1:100-400:0.8-4:0.5-3, preferably 1:150-300:1-3:0.8-2.5, more preferably 1:200-280:1.5-2.5: 1-2.
Preferably, step 1) is specifically: the anthranilic alcohol and the triphosgene are weighed according to the proportion and dissolved in an organic solvent, then alkali is added for reaction, the reaction temperature is 50-80 ℃ (60-68 ℃ is preferred), and the reaction time is 20-60min (30-40 min is preferred).
Preferably, step 2) is specifically: 3, 1-benzoxazine-2-one and 1, 2-dichloroethane are weighed according to the proportion and dissolved in an organic solvent, and then alkali and an optional catalyst (such as tetrabutylammonium iodide) are added for reaction at the temperature of 50-80 ℃ (preferably 55-65 ℃) for 5-15h (preferably 10-13 h).
Preferably, step 3) is specifically: weighing substituted aniline with a structural general formula (III) according to a proportion, dissolving the substituted aniline in an organic solvent, adding a phase transfer catalyst and alkali, and then carrying out acid-base salt formation reaction (preferably reflux reaction, the reaction temperature is 50-100 ℃, preferably 60-100 ℃, and the reaction time is 10-60min, preferably 20-40 min). After the reaction is completed, cooling (preferably to room temperature), then adding N- (2-chloroethyl) -3, 1-benzoxazine-2-one of formula (II) to continue the reaction (preferably reflux reaction, the reaction temperature is 50-100 ℃, preferably 60-90 ℃, the reaction time is 10-48h, preferably 20-30 h). Cooling (preferably to room temperature) to obtain a reaction mixture containing N- (arylaminoethyl) -3, 1-benzoxazine-2-one compounds.
Preferably, the step 4) is specifically: filtering (preferably, filtering) the reaction mixture containing the N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound obtained in the step 3), and washing (preferably, washing 1-8 times by using ethyl acetate, preferably 2-5 times) to obtain a filtrate. The filtrate is then dried (preferably over anhydrous Na)2SO4Drying), filtering (preferably suction filtration), and desolventizing (preferably desolventizing under reduced pressure). Finally, the N- (arylamino ethyl) -3, 1-benzoxazine-2-ketone compound is obtained after column chromatography separation.
According to a third embodiment of the invention, there is provided the use of the N- (arylaminoethyl) -3, 1-benzoxazin-2-ones of the general structural formula (I) described in the first embodiment or the N- (arylaminoethyl) -3, 1-benzoxazin-2-ones of the general structural formula (I) prepared by the process described in the second embodiment. The N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound with the structural general formula (I) is used for inhibiting one or more of wheat scab, cucumber gray mold, phytophthora capsici, sclerotinia sclerotiorum, rice sheath blight or rice blast.
In the present invention, N- (2-chloroethyl) -3, 1-benzoxazine-2-one (II) and substituted aniline (III) are reacted in the presence of an organic solvent (e.g. acetonitrile), a base (e.g. potassium carbonate), a phase transfer catalyst (e.g. sodium iodide) to obtain a reaction mixture comprising a compound having the general structural formula (I); then separating and purifying the reaction mixture containing the compound with the structural general formula (I) to finally obtain the N- (arylamino ethyl) -3, 1-benzoxazine-2-ketone compound with the structural general formula (I). The specific reaction process is as follows:
wherein, the R group on the compound with the structural general formula (I) is derived from a substituted R group on a substituted aniline. R is hydrogen or C1-C2Alkyl or halogen or C1-C2An alkoxy group. Preferably, R is selected from one of H, methyl, ethyl, F, Cl, Br, methoxy and ethoxy. More preferably, R is selected from H, 4-CH3、3-CH3、2-CH3、4-Cl、3-Cl、2-Cl、4-OCH3、3-OCH3、2-OCH3One kind of (1).
In the present invention, 3, 1-benzoxazine-2-one is obtained by reacting anthranilic alcohol with triphosgene in an organic solvent (e.g., tetrahydrofuran) and in the presence of a base (e.g., triethylamine):
in the present invention, the 3, 1-benzoxazine-2-one and 1, 2-dichloroethane obtained in step 1) are dissolved in an organic solvent (e.g., tetrahydrofuran), and then a base (e.g., cesium carbonate) and optionally a catalyst (e.g., tetrabutylammonium iodide in an appropriate amount, e.g., 0 to 40%, preferably 5 to 20% of the amount of the 3, 1-benzoxazine-2-one) are added to carry out a reaction to obtain N- (2-chloroethyl) -3, 1-benzoxazine-2-one having the formula (II):
in the present invention, optionally means carrying out or not, adding or not.
In the present invention, the selected chemical reagents and sources thereof are as follows:
compared with the prior art, the invention has the following beneficial technical effects:
1. the N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound with the general formula (I) is synthesized for the first time, and the compound has good bacteriostatic activity; especially has obvious effect of inhibiting the activity of the germs of wheat scab, cucumber gray mold, pepper phytophthora, sclerotinia sclerotiorum, rice sheath blight or rice blast.
2. The N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound with the general formula (I) prepared by the invention has the advantages of simple preparation method, cheap and easily obtained raw materials and high yield.
Drawings
FIG. 1 is a synthesis scheme of N- (arylaminoethyl) -3, 1-benzoxazine-2-ones of the general formula (I) of the present invention.
Detailed Description
The technical solution of the present invention is illustrated below, and the claimed scope of the present invention includes, but is not limited to, the following examples.
A process for the preparation of N- (arylaminoethyl) -3, 1-benzoxazin-2-ones having the general structural formula (I):
the preparation method comprises the following steps:
1) the reaction of anthranilic alcohol with triphosgene gives 3, 1-benzoxazine-2-one:
2) reacting the 3, 1-benzoxazine-2-one obtained in step 1) with 1, 2-dichloroethane to obtain N- (2-chloroethyl) -3, 1-benzoxazine-2-one having the structural formula (II):
3) reacting the N- (2-chloroethyl) -3, 1-benzoxazine-2-one of formula (II) obtained in step 2) with a substituted aniline of general structural formula (III) to obtain a reaction mixture comprising N- (arylaminoethyl) -3, 1-benzoxazine-2-one compounds of general structural formula (I):
4) separating and purifying the reaction mixture containing the N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound with the structural general formula (I) obtained in the step 3) to obtain the N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound with the structural general formula (I).
Preferably, R is hydrogen or C1-C2Alkyl or halogen or C1-C2An alkoxy group.
Preferably, R is selected from one of H, methyl, ethyl, F, Cl, Br, methoxy and ethoxy.
Preferably, R is selected from H, 4-CH3、3-CH3、2-CH3、4-Cl、3-Cl、2-Cl、4-OCH3、3-OCH3、2-OCH3One kind of (1).
Preferably, in step 1), the anthranilic alcohol is reacted with triphosgene in an organic solvent and in the presence of a base.
Preferably, in step 1), the organic solvent is one of tetrahydrofuran, toluene and 1, 2-dichloroethane. Tetrahydrofuran is preferred.
Preferably, in step 1), the base is triethylamine or pyridine. Triethylamine is preferred.
Preferably, in step 2), the 3, 1-benzoxazine-2-one and 1, 2-dichloroethane are reacted in an organic solvent and in the presence of a base.
Preferably, in step 2), the organic solvent is tetrahydrofuran or toluene. Tetrahydrofuran is preferred.
Preferably, in step 2), the base is cesium carbonate or potassium carbonate. Cesium carbonate is preferred.
Preferably, in step 3), the N- (2-chloroethyl) -3, 1-benzoxazine-2-one and substituted aniline are reacted in an organic solvent in the presence of a base and a phase transfer catalyst.
Preferably, in step 3), the organic solvent is acetonitrile or Dimethylformamide (DMF). Acetonitrile is preferred.
Preferably, in step 3), the base is potassium carbonate or NaOH. Preferably potassium carbonate.
Preferably, the phase transfer catalyst is sodium iodide or tetrabutyl ammonium iodide. Sodium iodide is preferred.
Preferably, the anthranilic alcohol, triphosgene, organic solvent and base are added in step 1) in a molar ratio of 1:0.5-1.5:30-120:0.8-3, preferably 1:0.8-1.2:40-100: 1-2.
Preferably, in step 2), the 3, 1-benzoxazine-2-one, 1, 2-dichloroethane, the organic solvent and the base are added in a molar ratio of 1:2-4:20-100:0.5-3, preferably 1:2.5-3.5:30-80: 1-2.5.
Preferably, in step 3), the molar ratio of the N- (2-chloroethyl) -3, 1-benzoxazin-2-one of formula (II) to the amount of substituted aniline of general structural formula (III) added is 1:0.5 to 2, preferably 1:0.8 to 1.8, more preferably 1:1.0 to 1.5.
Preferably, the molar ratio of the N- (2-chloroethyl) -3, 1-benzoxazine-2-one, the organic solvent, the base and the phase transfer catalyst is 1:100-400:0.8-4:0.5-3, preferably 1:150-300:1-3:0.8-2.5, more preferably 1:200-280:1.5-2.5: 1-2.
Preferably, step 1) is specifically: the anthranilic alcohol and the triphosgene are weighed according to the proportion and dissolved in an organic solvent, then alkali is added for reaction, the reaction temperature is 50-80 ℃ (60-68 ℃ is preferred), and the reaction time is 20-60min (30-40 min is preferred).
Preferably, step 2) is specifically: weighing 3, 1-benzoxazine-2-one according to a certain proportion, dissolving in 1, 2-dichloroethane, reacting, adding alkali and optionally catalyst (such as tetrabutylammonium iodide), reacting at 50-80 deg.C (preferably 55-65 deg.C) for 5-15h (preferably 10-13 h).
Preferably, the step 3) is specifically as follows: weighing substituted aniline with a general structural formula (III) according to a proportion, dissolving the substituted aniline in an organic solvent, adding a phase transfer catalyst and alkali, and then carrying out a reaction, preferably a reflux reaction, wherein the reaction temperature is 50-100 ℃, preferably 60-100 ℃. The reaction time is 10-60min, preferably 20-40 min). After the reaction is completed, cooling (preferably to room temperature), then adding N- (2-chloroethyl) -3, 1-benzoxazine-2-one of formula (II) to continue the reaction (preferably reflux reaction, the reaction temperature is 50-100 ℃, preferably 60-90 ℃, the reaction time is 10-48h, preferably 20-30 h). Cooling (preferably to room temperature) to obtain a reaction mixture containing N- (arylaminoethyl) -3, 1-benzoxazine-2-one compounds.
Preferably, the step 4) is specifically as follows: will be described in detail3) The reaction mixture containing the N- (arylaminoethyl) -3, 1-benzoxazine-2-one compound obtained is filtered (preferably suction filtered) and washed (preferably 1 to 8 times, preferably 2 to 5 times with ethyl acetate) to obtain a filtrate. The filtrate is then dried (preferably over anhydrous Na)2SO4Drying), filtering (preferably suction filtration), and desolventizing (preferably desolventizing under reduced pressure). Finally, the N- (arylamino ethyl) -3, 1-benzoxazine-2-ketone compound is obtained after column chromatography separation.
Preparation examples
1) Preparation of 3, 1-benzoxazine-2-one: 10mmol of anthranilic alcohol and 6.5mmol of triphosgene are dissolved in 30mL of tetrahydrofuran, and then 20mmol of triethylamine is added to react for 30min at the temperature of 65 ℃ to obtain 3, 1-benzoxazine-2-ketone.
2) Preparation of N- (2-chloroethyl) -3, 1-benzoxazine-2-one: dissolving 5mmol of 3, 1-benzoxazine-2-one in 30mL of tetrahydrofuran, adding 15mmol of 1, 2-dichloroethane, then adding 10mmol of cesium carbonate and 1mmol of tetrabutylammonium iodide, and reacting at 65 ℃ for 12h to obtain N- (2-chloroethyl) -3, 1-benzoxazine-2-one.
Example 1
And (3) synthesizing N- ((4-toluidino) ethyl) -3, 1-benzoxazine-2-ketone.
0.35g (3.3mmol) of p-toluidine, 0.83g (6mmol) of potassium carbonate and 0.49g (3.3mmol) of sodium iodide were weighed out and put in a 100mL single-necked flask, 40mL of acetonitrile was added as a solvent, and a reflux reaction (temperature 80 ℃ C.) was carried out for 30 minutes and then cooled to room temperature. Then 0.63g (3mmol) of N- (2-chloroethyl) -3, 1-benzoxazine-2-one is added, the mixture is stirred and refluxed for reaction for 26 hours at the temperature of 80 ℃, and the mixture is cooled to the room temperature after the reaction is completed. The precipitate was filtered off and washed 3 times with ethyl acetate and the filtrate was collected. Finally, the obtained filtrate is decompressed, desolventized and subjected to column chromatography to obtain a white solid with a melting point (mp): 97.1-99.0 ℃, yield: 50.7 percent.
1H NMR(500MHz，CDCl3)δ7.45(dd，J＝7.2，1.9Hz，1H)，7.29-7.25(m，2H)，7.22–7.19(m，1H)，6.93(d，J＝8.2Hz，2H)，6.51(d，J＝8.4Hz，2H)，4.34–4.31(m，2H)，4.26(s，2H)，3.87–3.84(m，2H)，2.20(s，3H).
13C NMR(126MHz，CDCl3)δ156.85，145.61，137.14，135.48，129.48(2C)，129.33，128.19，128.03，126.43，126.32，112.81(2C)，62.28，48.03，44.75，20.13.
Example 2
And (3) synthesizing N- ((3-toluidino) ethyl) -3, 1-benzoxazine-2-ketone.
0.35g (3.3mmol) of m-toluidine, 0.83g (6mmol) of potassium carbonate and 0.49g (3.3mmol) of sodium iodide were weighed out and put in a 100mL single-necked flask, 40mL of acetonitrile was added as a solvent, and a reflux reaction (temperature 80 ℃ C.) was carried out for 30 minutes and then cooled to room temperature. Then 0.63g (3mmol) of N- (2-chloroethyl) -3, 1-benzoxazine-2-one is added, the mixture is stirred and refluxed for reaction for 26 hours at the temperature of 80 ℃, and the mixture is cooled to the room temperature after the reaction is completed. The precipitate was filtered off and washed 3 times with ethyl acetate and the filtrate was collected. Finally, the filtrate is decompressed, desolventized and subjected to column chromatography to obtain a white solid with a melting point (mp): 122.7-123.5 ℃, yield: 47.6 percent.
1H NMR(500MHz，CDCl3)δ7.48(dd，J＝7.3，1.8Hz，1H)，7.33-7.28(m，2H)，7.25–7.23(m，1H)，7.03(t，J＝7.7Hz，1H)，6.54(d，J＝7.5Hz，1H)，6.47(s，1H)，6.42(dd，J＝8.0，2.0Hz，1H)，4.44–4.40(m，2H)，4.31(s，2H)，3.95–3.92(m，2H)，2.24(s，3H).
13C NMR(126MHz，CDCl3)δ157.09，147.79，139.07，137.01，135.72，129.91，129.12，128.54，128.49，126.54，118.86，113.87，110.14，62.45，48.35，44.99，21.56.
Example 3
And (3) synthesizing N- ((2-toluidino) ethyl) -3, 1-benzoxazine-2-ketone.
0.35g (3.3mmol) of o-toluidine, 0.83g (6mmol) of potassium carbonate and 0.49g (3.3mmol) of sodium iodide were weighed out into a 100mL single-necked flask, 40mL of acetonitrile was added as a solvent, and a reflux reaction (temperature 80 ℃ C.) was carried out for 30 minutes and then cooled to room temperature. Then 0.63g (3mmol) of N- (2-chloroethyl) -3, 1-benzoxazine-2-one is added, the mixture is stirred and refluxed for reaction for 26 hours at the temperature of 80 ℃, and the mixture is cooled to the room temperature after the reaction is completed. The precipitate was filtered off and washed 3 times with ethyl acetate and the filtrate was collected. Finally, the filtrate is decompressed, desolventized and subjected to column chromatography to obtain a white solid with a melting point (mp): 111.0-113.0 ℃, yield: 44.4 percent.
1H NMR(500MHz，CDCl3)δ7.46(dd，J＝7.2，1.8Hz，1H)，7.33-7.28(m，2H)，7.25–7.20(m，1H)，7.07–7.04(m，2H)，6.65(t，J＝7.3Hz，1H)，6.56(d，J＝7.9Hz，1H)，4.38–4.36(m，2H)，4.35(s，3H)，3.91–3.88(m，2H)，2.13(s，3H).
13C NMR(126MHz，CDCl3)δ156.93，145.72，136.90，135.57，129.88，129.49，128.32，128.23，126.85，126.35，122.06，117.02，109.66，62.29，48.03，44.41，17.30.
Example 4
And (3) synthesizing N- ((anilino) ethyl) -3, 1-benzoxazine-2-ketone.
0.31g (3.3mmol) of aniline, 0.83g (6mmol) of potassium carbonate and 0.49g (3.3mmol) of sodium iodide were weighed into a 100mL single-necked flask, 40mL of acetonitrile was added as a solvent, and a reflux reaction (80 ℃ C.) was carried out for 30 minutes and then cooled to room temperature. Then 0.63g (3mmol) of N- (2-chloroethyl) -3, 1-benzoxazine-2-one is added, the mixture is stirred and refluxed for reaction for 26 hours at the temperature of 80 ℃, and the mixture is cooled to the room temperature after the reaction is completed. The precipitate was filtered off and washed 3 times with ethyl acetate and the filtrate was collected. Finally, the filtrate is decompressed, desolventized and subjected to column chromatography to obtain a white solid with a melting point (mp): 140.7-142.1 ℃, yield: 41.7 percent.
1H NMR(500MHz，CDCl3)δ7.48–7.47(m，1H)，7.30(td，J＝7.1，1.3Hz，2H)，7.26–7.23(m，1H)，7.14(t，J＝7.8Hz，2H)，6.70(t，J＝7.3Hz，1H)，6.60(d，J＝7.9Hz，2H)，4.38(t，J＝7.9Hz，2H)，4.32(s，2H)，3.91(t，J＝7.9Hz，2H).
13C NMR(126MHz，CDCl3)δ156.96，147.87，136.96，135.57，129.56，129.14(2C)，128.41，128.31，126.43，117.53，112.80(2C)，62.39，48.19，44.68.
Example 5
And (3) synthesizing N- ((4-chloroanilino) ethyl) -3, 1-benzoxazine-2-ketone.
0.42g (3.3mmol) of p-chloroaniline, 0.83g (6mmol) of potassium carbonate and 0.49g (3.3mmol) of sodium iodide were weighed out into a 100mL single-necked flask, 40mL of acetonitrile was added as a solvent, and a reflux reaction (temperature 80 ℃ C.) was carried out for 30 minutes and then cooled to room temperature. Then 0.63g (3mmol) of N- (2-chloroethyl) -3, 1-benzoxazine-2-one is added, the mixture is stirred and refluxed for reaction for 26 hours at the temperature of 80 ℃, and the mixture is cooled to the room temperature after the reaction is completed. The precipitate was filtered off and washed 3 times with ethyl acetate and the filtrate was collected. Finally, the filtrate is decompressed, desolventized and subjected to column chromatography to obtain a white solid with a melting point (mp): 125.8-126.6 ℃, yield: 43.3 percent.
1H NMR(500MHz，CDCl3)δ7.46(dd，J＝7.4，1.7Hz，1H)，7.36–7.31(m，2H)，7.27(dd，J＝7.4，1.7Hz，1H)，7.09(d，J＝2.1Hz，1H)，7.08(d，J＝2.1Hz，1H)，6.55–6.54(m，1H)，6.53–6.52(m，1H)，4.46–4.43(m，2H)，4.30(s，2H)，3.97–3.94(m，2H).
13C NMR(126MHz，CDCl3)δ156.98，146.44，136.47，135.55，129.48，128.94(2C)，128.47(2C)，126.34，122.00，113.95(2C)，62.44，48.16，44.75.
Example 6
And (3) synthesizing N- ((3-chloroanilino) ethyl) -3, 1-benzoxazine-2-ketone.
0.42g (3.3mmol) of m-chloroaniline, 0.83g (6mmol) of potassium carbonate and 0.49g (3.3mmol) of sodium iodide were weighed out and put in a 100mL single-necked flask, 40mL of acetonitrile was added as a solvent, and a reflux reaction was carried out (temperature: 80 ℃ C.) for 30 minutes and then cooled to room temperature. Then 0.63g (3mmol) of N- (2-chloroethyl) -3, 1-benzoxazine-2-one is added, the mixture is stirred and refluxed for reaction for 26 hours at the temperature of 80 ℃, and the mixture is cooled to the room temperature after the reaction is completed. The precipitate was filtered off and washed 3 times with ethyl acetate and the filtrate was collected. Finally, the filtrate is decompressed, desolventized and subjected to column chromatography to obtain a white solid with a melting point (mp): 158.0-159.3 ℃, yield: 41.1 percent.
1H NMR(500MHz，CDCl3)δ7.44(dd，J＝7.3，1.4Hz，1H)，7.35–7.28(m，2H)，7.25–7.23(m，1H)，7.03(t，J＝8.0Hz，1H)，6.66–6.64(m，1H)，6.58(t，J＝1.9Hz，1H)，6.48(dd，J＝8.2，2.1Hz，1H)，4.47–4.44(m，2H)，4.29(s，2H)，3.97–3.94(m，2H).
13C NMR(126MHz，CDCl3)δ157.12，148.78，136.17，135.73，134.96，130.28，129.90，128.74，128.62，126.30，117.84，112.73，111.56，62.52，48.28，44.87.
Example 7
And (3) synthesizing N- ((2-chloroanilino) ethyl) -3, 1-benzoxazine-2-ketone.
0.42g (3.3mmol) of o-chloroaniline, 0.83g (6mmol) of potassium carbonate and 0.49g (3.3mmol) of sodium iodide were weighed out and put in a 100mL single-necked flask, 40mL of acetonitrile was added as a solvent, and a reflux reaction was carried out (temperature: 80 ℃ C.) for 30 minutes and then cooled to room temperature. Then 0.63g (3mmol) of N- (2-chloroethyl) -3, 1-benzoxazine-2-one is added, the mixture is stirred and refluxed for reaction for 26 hours at the temperature of 80 ℃, and the mixture is cooled to the room temperature after the reaction is completed. The precipitate was filtered off and washed 3 times with ethyl acetate and the filtrate was collected. Finally, the filtrate is decompressed, desolventized and subjected to column chromatography to obtain a white solid with a melting point (mp): 105.2-107.0 ℃, yield: 38.8 percent.
1H NMR(500MHz，CDCl3)δ7.43(dd，J＝7.3，1.6Hz，1H)，7.32-7.28(m，2H)，7.25–7.22(m，2H)，7.06(td，J＝7.9，1.4Hz，1H)，6.61(dd，J＝12.0，4.5Hz，2H)，4.42(s，2H)，4.42–4.38(m，2H)，3.93–3.90(m，2H).
13C NMR(126MHz，CDCl3)δ156.60，143.40，136.21，135.58，129.15，128.97，128.37，128.35，127.80，126.24，118.90，117.49，111.42，62.38，48.09，44.30.
Example 8
And (3) synthesizing N- ((4-methoxyanilino) ethyl) -3, 1-benzoxazine-2-ketone.
0.41g (3.3mmol) of p-anisidine, 0.83g (6mmol) of potassium carbonate and 0.49g (3.3mmol) of sodium iodide were weighed and put in a 100mL single-necked flask, 40mL of acetonitrile was added as a solvent, and a reflux reaction (temperature 80 ℃ C.) was carried out for 30 minutes and then cooled to room temperature. Then 0.63g (3mmol) of N- (2-chloroethyl) -3, 1-benzoxazine-2-one is added, the mixture is stirred and refluxed for reaction for 26 hours at the temperature of 80 ℃, and the mixture is cooled to the room temperature after the reaction is completed. The precipitate was filtered off and washed 3 times with ethyl acetate and the filtrate was collected. Finally, the filtrate is decompressed, desolventized and subjected to column chromatography to obtain a red oily compound, wherein the yield is as follows: 58.3 percent.
1H NMR(500MHz，CDCl3)δ7.41(dd，J＝7.2，1.8Hz，1H)，7.26-7.22(m，2H)，7.18(dd，J＝7.2，1.9Hz，1H)，6.68–6.67(m，2H)，6.52–6.50(m，2H)，4.34–4.31(m，2H)，4.20(s，2H)，3.86–3.83(m，2H)，3.63(s，3H).
13C NMR(126MHz，CDCl3)δ156.96，152.00，142.09，137.14，135.53，129.53，128.30，128.18，126.40，114.64(2C)，114.07(2C)，62.35，55.53，48.15，45.49.
Example 9
And (3) synthesizing N- ((3-methoxyanilino) ethyl) -3, 1-benzoxazine-2-ketone.
0.41g (3.3mmol) of m-anisidine, 0.83g (6mmol) of potassium carbonate and 0.49g (3.3mmol) of sodium iodide were weighed into a 100mL single-necked flask, 40mL of acetonitrile was added as a solvent, and a reflux reaction (temperature 80 ℃ C.) was carried out for 30 minutes and then cooled to room temperature. Then 0.63g (3mmol) of N- (2-chloroethyl) -3, 1-benzoxazine-2-one is added, the mixture is stirred and refluxed for reaction for 26 hours at the temperature of 80 ℃, and the mixture is cooled to the room temperature after the reaction is completed. The precipitate was filtered off and washed 3 times with ethyl acetate and the filtrate was collected. Finally, carrying out decompression desolventizing on the filtrate, and carrying out column chromatography to obtain a yellow solid, wherein the melting point (mp) is 110.5-112.0 ℃, and the yield is as follows: and 55 percent.
1H NMR(500MHz，CDCl3)δ7.49–7.48(m，1H)，7.32(td，J＝6.6，1.6Hz，2H)，7.27–7.25(m，1H)，7.06(t，J＝8.1Hz，1H)，6.28(dd，J＝8.1，1.9Hz，1H)，6.24(dd，J＝8.0，1.6Hz，1H)，6.17(d，J＝2.0Hz，1H)，4.44–4.41(m，2H)，4.32(s，2H)，3.96–3.93(m，2H)，3.73(s，3H).
13C NMR(126MHz，CDCl3)δ160.75，156.99，149.28，136.92，135.70，129.96，129.73，128.48，128.42，126.47，106.00，102.94，98.86，62.43，55.00，48.28，44.86.
Example 10
And (3) synthesizing N- ((2-methoxyanilino) ethyl) -3, 1-benzoxazine-2-ketone.
0.41g (3.3mmol) of o-anisidine, 0.83g (6mmol) of potassium carbonate and 0.49g (3.3mmol) of sodium iodide were weighed out and put in a 100mL single-necked flask, 40mL of acetonitrile was added as a solvent, and a reflux reaction (temperature 80 ℃ C.) was carried out for 30 minutes and then cooled to room temperature. Then 0.63g (3mmol) of N- (2-chloroethyl) -3, 1-benzoxazine-2-one is added, the mixture is stirred and refluxed for reaction for 26 hours at the temperature of 80 ℃, and the mixture is cooled to the room temperature after the reaction is completed. The precipitate was filtered off and washed 3 times with ethyl acetate and the filtrate was collected. Finally, the filtrate is decompressed, desolventized and subjected to column chromatography to obtain a red oily compound, wherein the yield is as follows: 53.3 percent.
1H NMR(500MHz，CDCl3)δ7.57(dd，J＝7.1，1.7Hz，1H)，7.41–7.37(m，2H)，7.34–7.32(m，1H)，6.91–6.85(m，2H)，6.75(td，J＝7.8，1.2Hz，1H)，6.64(dd，J＝7.8，1.0Hz，1H)，4.46(t，J＝7.9Hz，4H)，4.00–3.97(m，2H)，3.91(s，3H).
13C NMR(126MHz，CDCl3)δ156.66，146.55，137.56，137.01，135.50，129.19，128.20，128.05，126.31，121.05，116.56，109.81，109.20，62.27，55.20，48.08，44.13.
Activity Effect test examples
By an ex vivo method, to N- ((4-toluidino) ethyl) -3, 1-benzoxazin-2-one, N- ((3-toluidino) ethyl) -3, 1-benzoxazin-2-one, N- ((2-toluidino) ethyl) -3, 1-benzoxazin-2-one, N- ((anilino) ethyl) -3, 1-benzoxazin-2-one, N- ((4-chloroanilino) ethyl) -3, 1-benzoxazin-2-one, N- ((3-chloroanilino) ethyl) -3, 1-benzoxazin-2-one, N- ((2-chloroanilino) ethyl) -3, bactericidal activity tests were carried out on 1-benzoxazin-2-one, N- ((4-methoxyanilino) ethyl) -3, 1-benzoxazin-2-one, N- ((3-methoxyanilino) ethyl) -3, 1-benzoxazin-2-one, N- ((2-methoxyanilino) ethyl) -3, 1-benzoxazin-2-one.
The materials for the bactericidal activity test are wheat scab, cucumber gray mold, phytophthora capsici, sclerotinia sclerotiorum, rice sheath blight and rice blast. The drug concentration was 50. mu.g/mL.
The bactericidal activity test results are shown in table one. As can be seen from Table I, the target compound has good inhibitory activity against the test germs. Wherein, the inhibition rate of N- (2- (4-methoxyanilino) ethyl) -3, 1-benzoxazine-2-ketone on phytophthora capsici is 100%, and the inhibition rate of N- ((3-chloroanilino) ethyl) -3, 1-benzoxazine-2-ketone on botrytis cinerea is 57.4%.
TABLE-fungicidal Activity of N- (arylaminoethyl) -3, 1-benzoxazin-2-ones (inhibition/%)
Claims (15)
1. An N- (arylaminoethyl) -3, 1-benzoxazine-2-one compound characterized by: the compounds are of the general structural formula (I):
wherein, in the formula (I), R is hydrogen or C1-C2Alkyl or halogen or C1-C2An alkoxy group.
2. The compound of claim 1, wherein: and R is selected from one of H, methyl, ethyl, F, Cl, Br, methoxy and ethoxy.
3. The compound of claim 1, wherein: r is selected from H and 4-CH3、3-CH3、2-CH3、4-Cl、3-Cl、2-Cl、4-OCH3、3-OCH3、2-OCH3One kind of (1).
4. The compound of claim 1, wherein: the N- (arylamino ethyl) -3, 1-benzoxazine-2-ketone compound is one or more compounds selected from the following compounds:
n- ((4-methylanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((3-methylanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((2-methylanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((anilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((4-chloroanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((3-chloroanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((2-chloroanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((4-methoxyanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((3-methoxyanilino) ethyl) -3, 1-benzoxazin-2-one:
n- ((2-methoxyanilino) ethyl) -3, 1-benzoxazin-2-one:
5. a process for the preparation of N- (arylaminoethyl) -3, 1-benzoxazin-2-ones of the general structural formula (I) as claimed in any one of claims 1 to 4:
the preparation method comprises the following steps:
1) the reaction of anthranilic alcohol with triphosgene gives 3, 1-benzoxazine-2-one:
2) reacting the 3, 1-benzoxazine-2-one obtained in step 1) with 1, 2-dichloroethane to obtain N- (2-chloroethyl) -3, 1-benzoxazine-2-one having the structural formula (II):
3) reacting the N- (2-chloroethyl) -3, 1-benzoxazine-2-one of formula (II) obtained in step 2) with a substituted aniline of general structural formula (III) to obtain a reaction mixture comprising N- (arylaminoethyl) -3, 1-benzoxazine-2-one compounds of general structural formula (I):
4) separating and purifying the reaction mixture containing the N- (arylaminoethyl) -3, 1-benzoxazine-2-one compound with the structural general formula (I) obtained in the step 3) to obtain the N- (arylaminoethyl) -3, 1-benzoxazine-2-one compound with the structural general formula (I);
wherein: r is as defined in any one of claims 1 to 4.
6. The method of claim 5, wherein: in step 1), the anthranilic alcohol is reacted with triphosgene in an organic solvent and in the presence of a base; the organic solvent is one of tetrahydrofuran, toluene and 1, 2-dichloroethane; the alkali is triethylamine or pyridine; and/or
In the step 2), the 3, 1-benzoxazine-2-one and 1, 2-dichloroethane are reacted in an organic solvent and in the presence of a base; the organic solvent is tetrahydrofuran or toluene; the alkali is cesium carbonate or potassium carbonate; and/or
In the step 3), the N- (2-chloroethyl) -3, 1-benzoxazine-2-one and substituted aniline react in an organic solvent in the presence of a base and a phase transfer catalyst; the organic solvent is acetonitrile or Dimethylformamide (DMF); the alkali is potassium carbonate or NaOH; the phase transfer catalyst is sodium iodide or tetrabutyl ammonium iodide.
7. The method of claim 6, wherein: in step 1), the organic solvent is tetrahydrofuran; the base is triethylamine; and/or
In step 2), the organic solvent is tetrahydrofuran; the base is cesium carbonate; and/or
In step 3), the organic solvent is acetonitrile; the alkali is potassium carbonate; the phase transfer catalyst is sodium iodide.
8. The method of claim 6, wherein: the molar ratio of the addition amounts of the anthranilic alcohol, the triphosgene, the organic solvent and the base in the step 1) is 1:0.5-1.5:30-120: 0.8-3; and/or
In the step 2), the molar ratio of the added amounts of the 3, 1-benzoxazine-2-one, the 1, 2-dichloroethane, the organic solvent and the base is 1:2-4:20-100: 0.5-3; and/or
In step 3), the molar ratio of the N- (2-chloroethyl) -3, 1-benzoxazine-2-one with the structural formula (II) to the added amount of the substituted aniline with the structural general formula (III) is 1: 0.5-2;
in the step 3), the molar ratio of the N- (2-chloroethyl) -3, 1-benzoxazine-2-one, the organic solvent, the base and the phase transfer catalyst is 1:100-400:0.8-4: 0.5-3.
9. The method of claim 6, wherein: the molar ratio of the addition amounts of the anthranilic alcohol, the triphosgene, the organic solvent and the base in the step 1) is 1:0.8-1.2:40-100: 1-2; and/or
In the step 2), the molar ratio of the addition amounts of the 3, 1-benzoxazine-2-one, the 1, 2-dichloroethane, the organic solvent and the base is 1:2.5-3.5:30-80: 1-2.5; and/or
In step 3), the molar ratio of the N- (2-chloroethyl) -3, 1-benzoxazine-2-one of formula (II) to the amount of substituted aniline of general structural formula (III) added is 1: 0.8-1.8;
in the step 3), the molar ratio of the N- (2-chloroethyl) -3, 1-benzoxazine-2-one, the organic solvent, the base and the phase transfer catalyst is 1:150-300:1-3: 0.8-2.5.
10. The method of claim 8, wherein: the step 1) is specifically as follows: weighing anthranilic alcohol and triphosgene according to a certain proportion, dissolving in an organic solvent, and then adding alkali to react at the temperature of 50-80 ℃ for 20-60 min; and/or
The step 2) is specifically as follows: weighing 3, 1-benzoxazine-2-one and 1, 2-dichloroethane according to a certain proportion, dissolving in an organic solvent, then adding alkali and optionally a catalyst for reaction, wherein the reaction temperature is 50-80 ℃, and the reaction time is 5-15 h; and/or
The step 3) is specifically as follows: weighing substituted aniline with a general structural formula (III) according to a proportion, dissolving the substituted aniline in an organic solvent, adding a phase transfer catalyst and alkali, and then reacting; after the reaction is finished, cooling, and then adding N- (2-chloroethyl) -3, 1-benzoxazine-2-ketone with a structural formula (II) for continuous reaction; cooling to obtain a reaction mixture containing N- (arylamino ethyl) -3, 1-benzoxazine-2-ketone compounds.
11. The method of claim 10, wherein: the reaction temperature in the step 1) is 60-68 ℃, and the reaction time is 30-40 min;
the catalyst in the step 2) is tetrabutylammonium bromide, the reaction temperature is 55-65 ℃, and the reaction time is 10-13 h; and/or
In the step 3), the reaction is carried out after adding a phase transfer catalyst and alkali, and specifically comprises the following steps: reflux reaction at 50-100 deg.c for 10-60 min; the continuous reaction by adding N- (2-chloroethyl) -3, 1-benzoxazine-2-ketone with the structural formula (II) is specifically as follows: reflux reaction at 50-100 deg.c for 10-48 hr; the cooling is to room temperature.
12. The method of claim 10, wherein: in the step 3), adding a phase transfer catalyst and alkali, and then reacting at the reaction temperature of 60-100 ℃ for 20-40 min; the reaction temperature of the continuous reaction of adding N- (2-chloroethyl) -3, 1-benzoxazine-2-ketone with the structural formula (II) is 60-90 ℃, and the reaction time is 20-30 h.
13. The method of claim 10, wherein: the step 4) is specifically as follows: filtering the reaction mixture containing the N- (arylaminoethyl) -3, 1-benzoxazine-2-ketone compound obtained in the step 3), and washing to obtain a filtrate; then drying, filtering and desolventizing the filtrate in sequence; finally, the N- (arylamino ethyl) -3, 1-benzoxazine-2-ketone compound is obtained after column chromatography separation.
14. The method of claim 13, wherein: in the step 4), the filtration is performed by suction filtration, and the washing is performed for 1-8 times by using ethyl acetate; the drying adopts anhydrous Na2SO4Drying; the desolventizing is decompression desolventizing.
15. Use of a N- (arylaminoethyl) -3, 1-benzoxazine-2-one compound according to any one of claims 1 to 4 wherein: the N- (arylaminoethyl) -3, 1-benzoxazine-2-one compound is used for inhibiting one or more of wheat scab, cucumber gray mold, phytophthora capsici leonian, sclerotinia sclerotiorum, rice sheath blight or rice blast.
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| CN114230537B (en) * | 2022-01-26 | 2023-07-21 | 贵州省茶叶研究所 | 2H-1, 4-benzoxazine-3 (4H) -ketone compound containing propanolamine structure and application thereof |
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| CN104045604B (en) * | 2014-06-09 | 2016-03-09 | 湖南科技大学 | Have 3 of fungicidal activity, 4 (6)-two replace-1,3-benzoxazine-2-ketone compounds |
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