CN102617482A - Trifluoromethyl-containing pyrimidinamine compound, preparation method thereof, and application of trifluoromethyl-containing pyrimidinamine compound used as bacteriacide - Google Patents
Trifluoromethyl-containing pyrimidinamine compound, preparation method thereof, and application of trifluoromethyl-containing pyrimidinamine compound used as bacteriacide Download PDFInfo
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- CN102617482A CN102617482A CN2012100935132A CN201210093513A CN102617482A CN 102617482 A CN102617482 A CN 102617482A CN 2012100935132 A CN2012100935132 A CN 2012100935132A CN 201210093513 A CN201210093513 A CN 201210093513A CN 102617482 A CN102617482 A CN 102617482A
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Abstract
The invention relates to a 4-substituted phenyl-6-trifluoromethyl-2-amino pyrimidinamine compound which has a novel chemical structure and a general formula III, a synthesis method for the compound and the application of the compound used as bacteriacide. The method comprises the following steps of: reacting substituted phenyl methyl ketone used as an initial raw material and trifluoroacetic acid ethyl ester under catalysis of sodium alcoholate to generate 4,4,4-trifluoro-1-substituded phenylbutane-1,3-diketone, and reacting 4,4,4-trifluoro-1-substituded phenylbutane-1,3-diketone and guanidinium salt under an alkaline condition to generate a III series compound with the general formula III. The compound with the general formula III can inhibit growth of pathogenic bacteria such as rice sheath blight, rice bakanae disease, exserohilum turcicum, bipolaris maydis, curvulavia lunata, corn kernel rot, corn top rot pathogenic bacteria, fusarium graminearum, cotton anthracnose, bean fusarium, rape sclerotinia rot, botrytis cinerea, cucumber fusarium wilt pathogenic bacteria, cucumber brown rot pathogenic bacteria, cucumber scab pathogenic bacteria, hot pepper root rot pathogenic bacteria, kidney bean anthracnose bacteria, and pythium aphanidermatum. In the formula III, R is methyl, ethyl, methoxy group, fluorine, chlorine, bromine, trifluoromethyl and other groups, and the number of R is 1 to 3.
Description
Technical field
The present invention relates to a kind of agrochemicals, particularly a kind of 4-substituted-phenyl-6-trifluoromethyl-2-amino-metadiazine compound, compound method and as the purposes of sterilant.
Background technology
Pyrimidinamine compound is the unique sterilant of one type of mechanism of action; Such medicament under isolated condition to the anti-microbial effect of germ very a little less than; But on host plant, show good control effect, main mechanism is the biosynthesizing that suppresses the secretion of germ cell wall clastic enzyme and disturb methionine(Met).No cross resistances such as same triazole species, imidazoles, morpholine class, dicarboximide class, phenylpyrrole class.The principal item of using in producing now has phonetic mould amine (pyrimethanil,, existing Beyer Co., Ltd in 1992), is mainly used in and prevents and treats gray mold, and germ was very fast to its development of drug resistance in recent years; Mepanipyrim (mepanipyrim, nineteen ninety, Japanese combinatorial chemistry company); Be mainly used in and prevent and treat gray mold, Powdery Mildew, black spot etc.; Cyprodinil (cyprodinil,, Syngenta Co.,Ltd in 1994) is mainly used in prevents and treats gray mold, Powdery Mildew, black spot, leaf spot, glume blight etc.
A lot of about report in recent years with fungicidal activity pyrimidinamine compound, see from structure, mainly contain two big types of heterocycle miazines and substituted uracils, and in the majority with the aminopyrimidine structure in the substituted pyrimidines compounds.But about the report of the synthetic and fungicidal activity that contains the trifluoromethyl pyrimidine compounds seldom.2003, M ü ller etc. reported that compound 1 can good restraining rice blast fungus (Pyricularia oryzae) (US 006562833) under 200mg/L concentration.2004, report compounds 2 such as Nakajawa had good restraining active (US006818631) to melon and fruit corruption mould (Pythium aphanidermatum), Botrytis cinerea bacterium (Botrytis cinerea), rape sick nuclear germ (Sclerotinia sclerotiorum) under 100mg/L concentration.
1 2R=MeS, Et, pyrrolidin-2-one
Summary of the invention
The objective of the invention is the reactive group trifluoromethyl to be introduced pyrimidine heterocyclic for a kind of novel sterilant is provided, the 4-substituted-phenyl of synthesizing new-6-trifluoromethyl-2-amino-metadiazine compound, it has good fungicidal activity.
The trifluoromethyl pyrimidine ammoniate that contains provided by the invention, its concrete structure general formula III is following:
In the formula, R is methyl, ethyl, methoxyl group, fluorine, chlorine, bromine, trifluoromethyl group, and its number is 1-3.Synthetic route is following:
A.CF
3COOC
2H
5/ CH
3ONa, reflux, 1h; B. guanidinesalt/CH
3ONa, reflux, 8h;
In the formula, R is methyl, ethyl, methoxyl group, fluorine, chlorine, bromine, trifluoromethyl group, and its number is 1-3.
With substituted acetophenone (I) is starting raw material, reacts under sodium alkoxide catalysis with Trifluoroacetic Acid Ethyl Ester, generates 4,4,4-three fluoro-1-substituted-phenyl butane-1, and 3-diketone (II), the latter reacts the generation general formula with guanidinesalt again under alkaline condition be the III series compound.
Growth of pathogenic bacteria such as compound III is withered to the curved spore of rice banded sclerotial blight, rice bakanae disease, the big spot of corn, corn stigma, corn, mealie corruption, corn top rot, gibberella saubinetii, cotton anthrax, soybean reaping hook, rape sclerotium, ash arrhizus bacteria, cucumber, cucumber foxiness, the black star of cucumber, capsicum root-rot, Kidney bean anthrax, melon and fruit corruption are mould have the strongly inhibited effect.
Positively effect of the present invention: the reactive group trifluoromethyl is introduced pyrimidine heterocyclic, the 4-substituted-phenyl of synthesizing new-6-trifluoromethyl-2-amino-metadiazine compound, it has good fungicidal activity.
Embodiment
Synthesizing of instance 1.4-(2-fluorophenyl)-6-trifluoromethyl-2-aminopyrimidine (III-1)
Methyl alcohol 30mL is added in the single port bottle, sodium Metal 99.5 0.2mol is cut into fragmental and adds repeatedly on a small quantity that wherein to make sodium methoxide solution subsequent use at 0-5 ℃.With stirring in methyl alcohol 60mL, 2-fluoro acetophenone 0.1mol, the Trifluoroacetic Acid Ethyl Ester 0.15mol adding there-necked flask, in there-necked flask, slowly drip sodium methylate then in addition, the control reacting liquid temperature is below 30 ℃ in the dropping process.Dropwise back temperature rising reflux 1h.Reaction solution left standstill be cooled to room temperature, pressure reducing and steaming 50mL methyl alcohol is poured in the 100mL frozen water that contains 30mL hydrochloric acid, stirs with glass stick, has a large amount of yellow solids to separate out, suction filtration, washing, drying, 4,4,4-three fluoro-1-(2-fluorophenyl) butane-1,3-diketone.
The methyl alcohol 60mL solution and the Guanidinium carbonate 0.13mol that will contain sodium Metal 99.5 0.15mol add in the there-necked flask, are heated to backflow, in reaction solution, add 4,4,4-three fluoro-1-(2-fluorophenyl) butane-1,3-diketone 0.085mol, back flow reaction 8h.In reaction solution, drip glacial acetic acid conditioned reaction liquid pH value to pH=4-5, occur a large amount of white precipitates in the reaction solution, suction filtration, washing, drying obtains pure article with recrystallizing methanol.Yield: 83%; Mp 116-117 ℃;
1H NMR (300MHz, CDCl
3), δ (ppm): 5.45 (br, 2H, NH
2), 7.18-8.10 (m, 5H, C
6H
4+ py-H); IR (KBr), v (cm
-1): 3324,3210 (NH
2), 1634 (C=N), 1585 (phenyl ring).
According to synthetic other the III-2～III-15 that obtains of above-mentioned method.The physicochemical data of compound is seen table 1, and the POP data are seen table 2.
The structure of table 1 compound III-1～III-15, physicochemical data and yield
The proton nmr spectra of table 2 compound III-1～III-15 (
1H NMR), ir spectra (IR) data
The fungicidal activity preliminary screening of instance 2. compound III-1～III-15
Adopt the mycelial growth rate method, measure target compound fungicidal activity to confession examination pathogenic fungi under 50mg/L.Each pathogenic bacteria that is grown on the PDA substratum is processed the bacterium piece with the punch tool of diameter 6mm, be inoculated on the toxic PDA substratum, after cultivating 3～5d under 23 ℃ ± 1 ℃, measure colony diameter, calculate inhibiting rate by (1) formula with the right-angled intersection method.
Inhibiting rate (%)=(blank colony diameter-toxic medium colony diameter)/(blank colony diameter-bacterium cake diameter) * 100 (1)
Tested the fungicidal activity of compound to 8 kinds of pathogenic bacterias, test-results is seen table 3.Under 50 μ g/mL concentration, compound III-1, III-2, III-5, III-6, III-10 have shown higher inhibition activity to a plurality of pathogenic bacterias, and be particularly better to the activity of tomato gray mould, gibberella saubinetii, corn stigma.Wherein III-1 and III-10 all are higher than 60% to the inhibiting rate of all pathogenic bacterias, and the activity of six kinds of pathogenic bacterias is higher than contrast medicament m-tetrachlorophthalodinitrile.From structure activity relationship, obviously help the raising of fungicidal activity when 2-contains substituting group in the position on phenyl ring.
Table 3 compound thing III-1～III-15 is to the inhibition active (50 μ g/mL) of 8 kinds of pathogenic bacterias
Instance 3. compound III-1～III-15 is to the accurate toxicity test of Botrytis cinerea germ
Adopt the mycelial growth rate method, measured the virulence of 15 new compounds to the Botrytis cinerea germ, test-results is seen table 4.With sample compound be configured to respectively that concentration is 100,25,6.25,1.56, the 0.39mg/L toxic substratum of totally five gradients.Use cyprodinil to be the contrast medicament, it is blank that acetone is set, triplicate.Utilize the statistical method of EXCEL software to calculate EC
50, EC
80Value, relatively medicament virulence size.
EC from table 3
50And EC
80Data can find out, the fungicidal activity that chemical combination III-1, III-10, III-13 will be higher than contrast medicament cyprodinil, particularly III-10 to the virulence of Botrytis cinerea germ is apparently higher than other compound.
Table 4 compound III-1～III-15 is to the toxicity test of Botrytis cinerea germ
| Compound number | Virulence regression equation | r | EC 50(μg/mL) | EC 80(μg/mL) |
| III-1 | y＝4.09+0.98x | 0.9638 | 8.24 | 59.15 |
| III-2 | y＝3.60+1.06x | 0.9923 | 20.30 | 125.52 |
| III-3 | y＝3.24+0.60x | 0.9958 | 846.88 | ＞10 3 |
| III-4 | y＝3.45+0.67x | 0.9934 | 202.19 | ＞10 3 |
| III-5 | y＝4.70+0.24x | 0.7739 | 16.31 | ＞10 3 |
| III-6 | y＝3.63+0.77x | 0.9891 | 57.14 | 695.71 |
| III-7 | y＝3.09+0.86x | 0.9795 | 155.55 | ＞10 3 |
| III-8 | y＝3.36+0.40x | 0.9586 | ＞10 3 | ＞10 3 |
| III-9 | y＝3.69+0.78x | 0.9829 | 46.50 | 555.31 |
| III-10 | y＝5.05+0.61x | 0.9742 | 0.80 | 19.18 |
| III-11 | y＝3.72+0.61x | 0.9292 | 120.45 | ＞10 3 |
| III-12 | y＝3.85+0.62x | 0.9989 | 69.38 | ＞10 3 |
| III-13 | y＝4.76+0.44x | 0.9298 | 3.40 | 277.84 |
| III-14 | y＝3.64+0.83x | 0.9700 | 42.88 | 441.43 |
| III-15 | y＝3.42+0.54x | 0.9564 | 808.74 | ＞10 3 |
| Cyprodinil | y＝4.33+0.65x | 0.9887 | 10.40 | 204.26 |
The accurate toxicity test of instance 4. compound III-1 pair 15 kinds of pathogenic bacterias
Adopt the mycelial growth rate method; Measured that compound III-1 pair rice banded sclerotial blight, rice bakanae disease, the big spot of corn, corn stigma, the curved spore of corn, mealie corruption, corn top rot, soybean reaping hook, rape sclerotium, cucumber are withered, the virulence of cucumber foxiness, the black star of cucumber, capsicum root-rot, Kidney bean anthrax, the mould 15 kinds of pathogenic bacterias of melon and fruit corruption, test-results is seen table 4.With sample compound be configured to respectively that concentration is 50,25,12.5,6.25,3.125, the 1.5625mg/L toxic substratum of totally six gradients.Adopt m-tetrachlorophthalodinitrile to be the contrast medicament, it is blank that acetone solvent is set, triplicate.Utilize the statistical method of EXCEL software to calculate EC
50, EC
90Value, relatively medicament virulence size.
See table 5, compound III-1 has very wide fungicidal spectrum, 15 kinds of pathogenic bacterias being tested has all been shown very high fungicidal activity, to the EC of all pathogenic bacterias
50Value is less than 50 μ g/mL.Wherein to the EC of 6 kinds of pathogenic bacterias
50Value is less than 10 μ g/mL, to the EC of 5 kinds of pathogenic bacterias
50Value is between 10 μ g/mL～20 μ g/mL, to the EC of 4 kinds of pathogenic bacterias
50Value is between 20 μ g/mL～50 μ g/mL, and the sterilization effect of rice banded sclerotial blight, Kidney bean anthrax, corn being bent spore, cucumber foxiness, the former bacterium of corn southern leaf blight is higher than contrast medicament m-tetrachlorophthalodinitrile, from the EC of medicament to pathogenic bacteria
80Value sees that fungistatic effect is more obvious when high density, generally is higher than contrast medicament m-tetrachlorophthalodinitrile.
The virulence of table 5 compound III-1 pair 15 kinds of pathogenic bacterias
Claims (3)
1. one kind contains the trifluoromethyl pyrimidine ammoniate, it is characterized in that chemical structure of general formula III is following:
In the formula, R is groups such as methyl, ethyl, methoxyl group, fluorine, chlorine, bromine, trifluoromethyl, and its number is 1-3.
2. compound method that contains the trifluoromethyl pyrimidine ammoniate according to claim 1 is characterized in that synthetic route is:
A.CF
3COOC
2H
5/ CH
3ONa, reflux, 1h; B. guanidinesalt/CH
3ONa, reflux, 8h;
In the formula, R is methyl, ethyl, methoxyl group, fluorine, chlorine, bromine, trifluoromethyl group, and its number is 1-3;
With substituted acetophenone (I) is starting raw material, reacts under sodium alkoxide catalysis with Trifluoroacetic Acid Ethyl Ester, generates 4,4,4-three fluoro-1-substituted-phenyl butane-1, and 3-diketone (II), the latter reacts the generation general formula with guanidinesalt again under alkaline condition be the III series compound.
3. one kind contains the trifluoromethyl pyrimidine ammoniate according to claim 1 as the disinfectant use in agriculture purposes, pathogenic bacteria such as it is characterized in that being used to prevent and treat that rice banded sclerotial blight, rice bakanae disease, the big spot of corn, corn stigma, the curved spore of corn, mealie corruption, corn top rot, gibberella saubinetii, cotton anthrax, soybean reaping hook, rape sclerotium, ash arrhizus bacteria, cucumber are withered, cucumber foxiness, the black star of cucumber, capsicum root-rot, Kidney bean anthrax, melon and fruit corruption are mould.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303048A (en) * | 2020-04-02 | 2020-06-19 | 沈阳农业大学 | Pyrimidine guanidine compound and preparation method and application thereof |
| CN115010641A (en) * | 2022-07-18 | 2022-09-06 | 青岛农业大学 | Beta-substituted pyrrole derivative, preparation method and application thereof |
| CN115197200A (en) * | 2022-06-29 | 2022-10-18 | 河南农业大学 | Trifluoromethyl tertiary alcohol and synthetic method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1287119A (en) * | 2000-09-18 | 2001-03-14 | 中国科学院广州化学研究所 | Synthesis of sylekirsey |
| CN1631882A (en) * | 2004-12-02 | 2005-06-29 | 江苏耕耘化学有限公司 | Preparation method of agricultural fungicide N-(4,6-dimethyl pyrimidine-2-yl) aniline |
-
2012
- 2012-04-01 CN CN201210093513.2A patent/CN102617482B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1287119A (en) * | 2000-09-18 | 2001-03-14 | 中国科学院广州化学研究所 | Synthesis of sylekirsey |
| CN1631882A (en) * | 2004-12-02 | 2005-06-29 | 江苏耕耘化学有限公司 | Preparation method of agricultural fungicide N-(4,6-dimethyl pyrimidine-2-yl) aniline |
Non-Patent Citations (4)
| Title |
|---|
| 《BULLETIONF THE CHEMICASLO CIETOYF JAPAN》 19691031 Tarozaemon NISHIWAKI Studies on Heterocyclic Chemistry. IV.1) Preparation of Several Trifluoromethyl-substituted Heterocyclic Compounds and Observation of Metastable Ion in the Mass Spectra of Trifluoromethyl-pyrazoles 3024-3026 2 第42卷, 第10期 * |
| CAS: "RN 710350-62-2", 《STN INTERNATIONAL》 * |
| TAROZAEMON NISHIWAKI: "Studies on Heterocyclic Chemistry. IV.1) Preparation of Several Trifluoromethyl-substituted Heterocyclic Compounds and Observation of Metastable Ion in the Mass Spectra of Trifluoromethyl-pyrazoles", 《BULLETIONF THE CHEMICASLO CIETOYF JAPAN》 * |
| 袁晶等: "2-氨基-6-三氟甲基嘧啶衍生物的合成及表征", 《化学研究与应用》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303048A (en) * | 2020-04-02 | 2020-06-19 | 沈阳农业大学 | Pyrimidine guanidine compound and preparation method and application thereof |
| CN111303048B (en) * | 2020-04-02 | 2023-05-26 | 沈阳农业大学 | Pyrimidine guanidine compound, and preparation method and application thereof |
| CN115197200A (en) * | 2022-06-29 | 2022-10-18 | 河南农业大学 | Trifluoromethyl tertiary alcohol and synthetic method and application thereof |
| CN115010641A (en) * | 2022-07-18 | 2022-09-06 | 青岛农业大学 | Beta-substituted pyrrole derivative, preparation method and application thereof |
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