CN107033081A - Formamide carbamide compounds of 3 difluoromethyl 1H pyrazoles of a kind of 1 methyl 4 and its preparation method and application - Google Patents
Formamide carbamide compounds of 3 difluoromethyl 1H pyrazoles of a kind of 1 methyl 4 and its preparation method and application Download PDFInfo
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
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Abstract
The invention discloses a kind of formamide carbamide compounds of 1 methyl, 3 difluoromethyl 1H pyrazoles 4 and preparation method thereof and the application in preventing and treating Cucumber Target Leaf Spot, cucumber bacterial angular leaf spot, cucumber fusarium axysporum, botrytis cinerea pers, it obtains the methyl acetoacetate of 24,4 difluoro of ethoxymeyhylene of intermediate (E) 3 by difluoro ethyl acetoacetate and triethyl orthoformate reaction；Intermediate successively with methyl hydrazine reaction, hydrolyze again after with ammoniacal liquor react to obtain the acid amides of 1 methyl, 3 difluoromethyl 1H pyrazoles 4；Finally anil reaction overnight respectively with oxalyl chloride and different substituents, reacts and terminates rear vacuum distillation, recrystallize to obtain target compound；The compounds of this invention is the noval chemical compound with bactericidal activity, is that the research and development of novel pesticide provide the foundation.
Description
Technical field
It is 1- methyl -3- difluoromethyl -1H- pyrazoles -4- first the present invention relates to a kind of acid amides carbamide compounds containing pyrazoles
Acid amides carbamide compounds and its preparation method and application.
Background technology
Pesticide industry enters fast-developing period since the eighties in last century, and novel pesticide emerges in an endless stream, wherein, jeterocyclic chemistry
Compound occupies highly important status.There is easing pain and diminishing inflammation from antipyrine of the Knott discoveries containing pyrazole ring in 1883 and move back
Heat effect；Nineteen fifty U.S. Rubbe, company developed the pyrazole compound with bactericidal activity.Pyrazole derivatives are as miscellaneous
An important class is even more to have critical role in new drug development field in cycle compound.Shown due to pyrazole compound
Efficiently, low toxicity and the characteristics of structure diversity, therefore its research and development is that agricultural chemicals and medicine add a new approach,
Cause the extensive concern of people.Many new, efficient, environment amenable pyrazole derivatives pesticide species also meet the tendency of and
Raw, such pesticides application scope is extremely extensive in the market, including weeding, desinsection/mite killing, sterilization and plant growth regulating etc.
Multiple fields.Successfully having developed multiple antiseptic kinds has：Greenery are peaceful, An Zhongning, the luxuriant peaceful, pyraclostrobin of leaf etc..Pyrazoles
The multiple biological activities that compound has, with boundless research and development prospect, people go deep into such compound
Research is underway always.Wherein, pyrazolecarboxamide compounds are due to containing two kinds of high activity building stones of pyrazoles and acid amides,
Concern with the excellent wider bioactivity, extremely people such as low toxicity, efficient, its MOLECULE DESIGN, synthesis and biology are lived
Journal of Sex Research is a focus of current pesticides discovery.Since 1940s, constantly there is document report in pesticide developing field
Road has the pyrazolecarboxamide analog derivative of bioactivity, including insecticide, acaricide, bactericide and herbicide etc., wherein having
It is pesticide new variety much successfully to be developed, for example, 1987, Mitsubishi Chemical Ind develops wide spectrum, new, efficient 5-
Pyrazol acid amide compounds tebufenpyrad；2000, E.I.Du Pont Company successfully developed a kind of efficient, low toxicity and mechanism of action is unique
Brand-new insecticide Rynaxypyr；2002, Mitsubishi Chemical Ind developed 5- pyrazole amide insecticides Tolfenpyrads,
Therefore the synthesis of pyrazol acid amide compounds has considerable value.
The content of the invention
It is an object of the present invention to provide a kind of 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamides carbamide compounds and its
Preparation method and application.
Described a kind of 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds, it is characterised in that it is tied
Shown in structure formula such as formula (I)：
In formula (I)：R is o-fluorophenyl, a fluorophenyl, 2,6- diethyl phenyls, 2,6- difluorophenyls, o-trifluoromethyl benzene
Base, Chloro-O-Phenyl, 3,5- 3,5-dimethylphenyls, 2,4,6- trimethylphenyls, adjacent Trifluoromethoxyphen-l, to ethylphenyl.
A kind of preparation method of described 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds, it is special
Levy and be to comprise the following steps that：
1) by difluoro ethyl acetoacetate and triethyl orthoformate in acetic anhydride back flow reaction, reaction terminate after depressurize steam
Evaporate to obtain compound shown in formula (II), the i.e. fluoro- 3- methyl acetoacetates of (E) -2- ethoxymeyhylenes -4,4- bis-；Then formula
(II) compound shown in and methyl hydrazine back flow reaction in ethanol, reaction terminate rear vacuum distillation, extract, obtain formula (III) institute
The compound shown；
2) by the compound hydrolysis shown in formula (III) obtain the compound shown in formula (IV), i.e. 1- methyl -3- difluoromethyls -
1H- pyrazoles -4- carboxylic acids；Compound and thionyl chloride back flow reaction shown in formula (IV), reaction terminate rear vacuum distillation and obtain formula (V)
Shown compound, i.e. 1- methyl -3- difluoromethyls -1H- pyrazoles -4- acyl chlorides；
3) compound shown in formula (V) is added in organic solvent, be then added dropwise in 25% ammoniacal liquor, room temperature is anti-
Should, obtain the compound shown in compound formula (VI), i.e. 1- methyl -3- difluoromethyls -1H- pyrazoles -4- acid amides；By formula (VI) Suo Shi
Compound be added in oxalyl chloride, be stirred at room temperature rear back flow reaction, reaction terminates rear vacuum distillation and obtains change shown in formula (VII)
Compound；
4) anil of the different substituents shown in formula (VIII) is added to having for the compound shown in formula (VII)
In machine solvent, reaction overnight, reaction terminates rear vacuum distillation, recrystallizes to obtain target compound shown in formula (I)；
In formula (VIII), X is monosubstituted or polysubstituted fluorine atom, chlorine atom, trifluoromethyl, trifluoromethoxy, methyl
Or ethyl.
A kind of preparation method of described 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds, it is special
Levy and be step 1) in the ratio between the amount of material of difluoro ethyl acetoacetate, triethyl orthoformate and acetic anhydride be 1:1.0~
2.0:The ratio between amount of material of compound and methyl hydrazine shown in 2.0~3.0. formulas (II) is 1:1.5~2.0, the volume of ethanol
Consumption is calculated as 0.5~1.0ml/mmol with the amount of the material of formula (II) compound.
A kind of preparation method of described 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds, it is special
Levy and be step 2) in alkali used in compound hydrolysis shown in formula (III) be potassium hydroxide or sodium hydroxide, the concentration of alkali is 4%
~6%, the ratio between amount of material of compound and thionyl chloride shown in formula (IV) is 1:8~15.
A kind of preparation method of described 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds, it is special
Levy and be step 3) in organic solvent be dichloromethane or chloroform, organic solvent volume consumption is with the change shown in formula (V)
The amount of the material of compound is calculated as 0.5~1.0ml/mmol.
A kind of preparation method of described 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds, it is special
Levy and be step 3) in the ratio between compound shown in formula (VI) and the amount of material of oxalyl chloride be 1:8~12.
A kind of preparation method of described 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds, it is special
Levy and be step 4) in organic solvent be dichloromethane, chloroform, acetone or tetrahydrofuran in one or more；It is organic
With formula, (amount of the material of the compound shown in (VII) is calculated as 0.1~0.3ml/mmol to solvent volume consumption.
A kind of preparation method of described 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds, it is special
Levy and be step 4) in the ratio between compound shown in formula (VII) and the amount of material of compound shown in formula (VIII) be 1:1.0
~1.5.
A kind of preparation method of described 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds, it is special
Levy and be step 4) in the used solvent of recrystallization be ethanol, ethyl acetate, petroleum ether, one or more of mixing in chloroform
Thing.
Described 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamides carbamide compounds are preparing preventing and treating cucumber foxiness
Application in disease, cucumber bacterium angular leaf spot, botrytis cinerea pers, cucumber fusarium axysporum bactericide.
The building-up process of the present invention is as follows：
Described 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamides carbamide compounds are preparing preventing and treating cucumber foxiness
Application in the bactericide such as germ, cucumber bacterial angular leaf spot bacterium, cucumber fusarium axysporum, botrytis cinerea pers.
Compared with prior art, the beneficial effects are mainly as follows：The invention provides a kind of 1- methyl -3-
Its preparation method and the application of difluoromethyl -1H- pyrazoles -4- formyls urea derivative and intermediate, the compound are with sterilization
The noval chemical compound of activity, is that the research and development of novel pesticide provide the foundation.
Embodiment
With reference to specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in
This：
The Carbox amide (I) containing pyrazoles of the present invention can be synthesized in the following manner：
1) synthesis of the 1- methyl -3- difluoromethyl -1H- pyrazoles -4- Ethyl formates described in formula (III)
By difluoro ethyl acetoacetate (40mmol), triethyl orthoformate (60mmol) is returned in acetic anhydride (0.12mol)
Stream reaction 8 hours, reaction terminates rear vacuum distillation, obtains crude product formula (II)；Under ice bath, formula (II) (40mmol) is instilled dropwise
Into methyl hydrazine (60mmol) and ethanol (20mL) mixed liquor, back flow reaction 6 hours, reaction terminates rear vacuum distillation, adds second
Acetoacetic ester (20mL) is extracted with saturated aqueous common salt, and organic layer is steamed with anhydrous sodium sulfate water removal rear overhang, obtains formula (III) 1- methyl -3-
Difluoromethyl -1H- pyrazoles -4- Ethyl formates.
2) 1- methyl -3- difluoromethyls -1H- pyrazoles -4- carbonyl isocyanates, the synthesis of formula (VII)
Formula (III) compound is added in 5% sodium hydrate aqueous solution, 60 DEG C are reacted 3 hours, then add hydrochloric acid
PH is adjusted to faintly acid by neutralization, and pumping rate obtains formula (IV) 1- methyl -3- difluoromethyl -1H- pyrazoles -4- carboxylic acids；Formula (IV) compound
(40mmol) and thionyl chloride (0.4mol) flow back 4 hours, vacuum distillation obtain formula (V) compound 1- methyl -3- difluoromethyls -
1H- pyrazoles -4- acyl chlorides；10mL dichloromethane is added in formula (V) compound, 25% ammoniacal liquor is then added dropwise to
In (0.32mol), react at room temperature 4 hours, reaction terminates rear vacuum distillation, and pumping rate obtains compound formula (VI) 1- methyl -3- difluoros
Methyl isophthalic acid H- pyrazoles -4- acid amides；Formula (VI) compound (10mmol) is added in oxalyl chloride (0.1mol), 1 is stirred at room temperature small
When after back flow reaction 5 hours, reaction terminates rear vacuum distillation and obtains formula (VII) compound.
3) N- carbanilinos -1- methyl -3- difluoromethyl -1H- pyrazole-4-carboxamide derivatives, the conjunction of formula (I)
Into
Formula (VII) compound (1mmol) is added in 10mL dichloromethane, anil (1.2mmol), room is added
Warm reaction overnight, reaction terminates rear vacuum distillation, recrystallizes to obtain target compounds of formula (I).
Embodiment 1
3- difluoromethyls-N- (o-fluorophenyl carbamoyl) -1- methyl isophthalic acid H- pyrazole-4-carboxamide white solids, production
Rate：32.3%, fusing point：233~234 DEG C,1H NMR(400MHz,CDCl3)δ:3.96 (s,3H,CH3), 6.85 (t, J=
54Hz,1H,F2CH), 7.00~7.07 (m, 2H, Ph), 7.31~7.33 (m, 1H, Ph), 7.98 (s, 1H, Ph), 8.34 (s,
1H,CH),10.13(s,1H,NH),10.33(s, 1H,NH)；HRMS(ESI)m/z:Calculated,313.0907,Found,
313.0903[M+H]+。
Embodiment 2
3- difluoromethyls-N- (a Fluorophenylamino formoxyl) -1- methyl isophthalic acid H- pyrazole-4-carboxamide white solids, production
Rate：83.9%, fusing point：233~234 DEG C,1H NMR(500MHz,d-DMSO)δ:3.96 (s,3H,CH3), 6.92~6.96 (m,
1H, Ph), 7.29 (t, J=54Hz, 1H, F2), CH 7.30~7.32 (m, 1H, Ph), 7.37~7.40 (m, 1H, Ph), 7.59
~7.62 (m, 1H, Ph), 8.68 (s, 1H, CH), 10.75 (s, 1H, NH), 10.95 (s, 1H, NH)；HRMS(ESI)m/z:
Calculated, 313.0907,Found,313.0904[M+H]+。
Embodiment 3
3- difluoromethyls-N- ((2,6- diethyl phenyls) carbamoyl) -1- methyl isophthalic acid H- pyrazole-4-carboxamides white
Solid, yield：79.3%, fusing point：211~212 DEG C,1H NMR(400MHz,d-DMSO) δ:1.23 (t, J=7.6Hz, 6H,
2CH3), 2.66~2.71 (m, 4H, 2CH2),3.54(s,3H,CH3), 6.86 (t, J=54Hz, 1H, F2), CH 7.21 (d, J=
7.2Hz, 2H, Ph), 7.31~7.35 (m, 1H, Ph), 8.35 (s, 1H, CH), 10.15 (s, 1H, NH), 10.98 (s, 1H,
NH)；HRMS(ESI)m/z: Calculated,331.0813,Found,331.0809[M+H]+。
Embodiment 4
3- difluoromethyls-N- ((2,6- difluorophenyls) carbamoyl) -1- methyl isophthalic acid H- pyrazole-4-carboxamides white is solid
Body, yield：71.8%, fusing point：241~242 DEG C,1H NMR(400MHz,d-DMSO) δ:3.99(s,3H,CH3),6.85(t,J
=54Hz, 1H, F2), CH 6.99~7.05 (m, 1H, Ph), 7.13~7.20 (m, 2H, Ph), 8.23 (s, 1H, CH), 9.04
(s,1H,NH),10.92(s,1H,NH)； HRMS(ESI)m/z:Calculated,331.0813,Found,331.0811[M+
H]+。
Embodiment 5
3- difluoromethyls-N- (o-trifluoromethyl phenylcarbamoyl) -1- methyl isophthalic acid H- pyrazole-4-carboxamides white is solid
Body, yield：36.1%, fusing point：221~222 DEG C,1H NMR(500MHz,d-DMSO) δ:3.96(s,3H,CH3),7.27(t,J
=53.5Hz, 1H, F2), CH 7.38 (d, J=8.0Hz, 1H, Ph), 7.70~7.77 (m, 2H, Ph), 8.11 (d, J=
8.0Hz,1H,Ph),8.71(s,1H,CH),11.02(s, 1H,NH),11.15(s,1H,NH)；HRMS(ESI)m/z:
Calculated,363.0875,Found, 363.0875[M+H]+。
Embodiment 6
3- difluoromethyls-N- (Chloro-O-Phenyl carbamoyl) -1- methyl isophthalic acid H- pyrazole-4-carboxamide white solids, production
Rate：50%, fusing point：210~211 DEG C,1H NMR(400MHz,d-DMSO)δ:3.97 (s,3H,CH3), 6.85 (t, J=54Hz,
1H,F2), CH 7.11~7.15 (m, 1H, Ph), 7.31~7.34 (m, 1H, Ph), 7.46~7.48 (m, 1H, Ph), 8.25~
8.28(m,1H,Ph),8.29(s,1H, CH),9.30(s,1H,NH),11.12(s,1H,NH)；HRMS(ESI)m/z:
Calculated, 329.0611,Found,329.0607[M+H]+。
Embodiment 7
3- difluoromethyls-N- ((2,5- 3,5-dimethylphenyls) carbamoyl) -1- methyl isophthalic acid H- pyrazole-4-carboxamides white
Solid, yield：53.5%, fusing point：207~208 DEG C,1H NMR(400MHz,d-DMSO) δ:2.35(s,6H,2CH3),3.85
(s,3H,CH3), 6.85 (s, 1H, Ph), 7.14 (t, J=54Hz, 1H, F2CH),7.19(s,2H,Ph),8.39(s,1H,CH),
9.89(s,1H,NH),10.69(s,1H, NH)；HRMS(ESI)m/z:Calculated,323.1314,Found,323.1314
[M+H]+。
Embodiment 8
3- difluoromethyls-N- ((2,4,6- trimethylphenyls) carbamoyl) -1- methyl isophthalic acid H- pyrazole-4-carboxamides are white
Color solid, yield：66.7%, fusing point：247~248 DEG C,1H NMR(500MHz, d-CDCl3)δ:2.28(s,6H,2CH3),
2.31(s,3H,CH3),3.62(s,3H,CH3), 6.85 (t, J=54Hz, 1H, F2CH),6.97(m,2H,Ph),8.35(s,
1H,CH),10.04(s,1H,NH), 10.86(s,1H,NH)；HRMS(ESI)m/z:Calculated,337.1471,Found,
337.1470 [M+H]+。
Embodiment 9
3- difluoromethyls-N- (adjacent Trifluoromethoxyphen-l carbamoyl) -1- methyl isophthalic acid H- pyrazole-4-carboxamides white
Solid, yield：66.5%, fusing point：177~178 DEG C,1H NMR(400MHz, d-DMSO)δ:3.95(s,3H,CH3),7.00
(t, J=54Hz, 1H, F2CH), 7.19~7.23 (m, 1H, Ph), 7.32~7.38 (m, 2H, Ph), 8.26 (d, J=9.2Hz,
1H,Ph),8.36(s,1H,CH),9.71 (s,1H,NH),11.27(s,1H,NH)；HRMS(ESI)m/z:Calculated,
379.0824,Found, 379.0823[M+H]+。
Embodiment 10
3- difluoromethyls-N- (to ethylphenyl carbamoyl) -1- methyl isophthalic acid H- pyrazole-4-carboxamide white solids,
Yield：68.8%, fusing point：239~240 DEG C,1H NMR(400MHz,d-DMSO)δ:1.26 (t, J=7.6Hz, 3H, CH3),
2.65~2.71 (m, 2H, CH2),3.88(s,3H,CH3), 7.18 (t, J=54.4Hz, 1H, F2), CH 7.23 (d, J=
8.4Hz, 2H, Ph), 7.46 (d, J=8.4Hz, 2H, Ph), 8.54 (s, 1H, CH), 10.40 (s, 1H, NH), 10.79 (s, 1H,
NH)；HRMS(ESI)m/z: Calculated,323.1314,Found,323.1302[M+H]+。
Embodiment 11
Bactericidal activity is tested
Subjects：Brown patch germ (Corynespora mazei), bacterial angular leaf spot bacterium (Pseudomonas
Syringae pv.lachrymans), ash arrhizus bacteria (Botrytis cinerea), wilt (Fusarium
oxysporum)。
For studying thing：Cucumber (Cucumis sativus L.), kind：" middle peasant No. 5 ".Arable farming and environmental condition：
Field management situation is identical with the cultivation management technology of the upper various vegetables in greenhouse of production, each cell cultivation management condition basic one
Cause.
Test medicine：The mother liquor that each compound is dissolved as 1.0g/L with DMF is standby, and concentration sets 50ppm (mg/L).
Comparison medicament (YCK)：Comparison medicament (YCK)：Cucumber Target Leaf Spot is 75% Bravo wettable powder (1500 times),
Cucumber bacterial angular leaf spot is 3% Zhongshengmycin wettable powder (1000 times), and cucumber fusarium axysporum is outstanding for 50% thiophanate-methyl
Floating agent (1500 times), gray mold of cucumber is 50% Boscalid water dispersible granules (1500 times).Separately set fluxapyroxad (FP), pyridine
Acyl bacterium amine (Bos) same concentrations are compareed；It is another to set solvent clear water (QCK) control.
Application method：Spraying equipment uses automatic fine sprayer.Spraying time and number of times are that cucumber two panels cotyledon period is applied
Medicine 1 time.Effective content according to reagent agent calculates the extension rate of experiment preparation, and medicament is prepared by experimental concentration, in
Cucumber seedling carries out spray pesticide (reagent agent and comparison medicament carry out spray pesticide) immediately after being unearthed, and reagent agent is uniform
The positive back side of blade is sprayed application to, is advisable with blade face droplet uniformity, is inoculated with 24 hours after dispenser.Cucumber Target Leaf Spot germ and ash
Mildew bacterium is inoculated with using spore suspension foliar spray, and angular leaf spot of cucumber is inoculated with using bacteria suspension foliar spray, moisturizing after inoculation
In case after moisturizing culture 24 hours, daytime Routine Management, night moist keeping measures.Cucumber fusarium axysporum uses radicle inoculation method, yellow
After melon vernalization 24h, when radicle length is to 0.5cm, 1h in the compound of various concentrations is immersed in, afterwards by seed from soak
Take out, be put into 4 degree of refrigerator overnights, next day takes out the cucumber seeds immersion 1 × 10 of dipped medicament from refrigerator5Individual spore/ml
Cucumber fusarium axysporum spore suspension in, immersion 30 minutes after be seeded in seedling alms bowl, in greenhouse Routine Management wait morbidity.Extremely
Investigated after clear water control morbidity fully.
Investigation method：Preventive effect is calculated according to the following grade scale investigation state of an illness.Control time and number of times are clear water to approved for distribution
After being ill, and when falling ill uniform investigate the state of an illness and calculate prevention effect.Sick leaf grade scale：0 grade：Disease-free spot；1 grade：Lesion area
Account for less than the 5% of whole leaf area；3 grades：Lesion area accounts for the 6%~10% of whole leaf area；5 grades：Lesion area is accounted for entirely
The 11%~25% of leaf area；7 grades：Lesion area accounts for the 26%~50% of whole leaf area；9 grades：Lesion area accounts for whole leaf
More than the 50% of area.
Drug effect computational methods：Column index formula is pressed according to disease index and calculates prevention effect, then it is newly multiple by Deng Kenshi
Range test (DMRT) method, the significance of difference of preventive effect between measure processing.
E series compound bactericidal activity test results are as shown in table 1 when concentration is 50ppm.
Each compound bactericidal activity test result of table 1
Each compound shows as one to cucumber aphid and cucumber fusarium axysporum under test result, 50ppm
Determine the facilitation of degree, the harm of disease is more beneficial for after administration；Inhibitory action is shown as to other two kinds of germs, wherein
E10 compounds show 57.11% prevention effect in the concentration to cucumber bacterial angular leaf spot, preventive effect and E1, E2, E3, E5,
E9 is higher than fluxapyroxad comparison medicine but less than Boscalid comparison medicine.In addition the prevention effect of E4, E6 to gray mold of cucumber
It has been higher than Boscalid and comparison medicine, but not as good as fluxapyroxad.
Claims (10)
1. a kind of 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds, it is characterised in that its structural formula such as formula
(I) shown in：
In formula (I)：R is o-fluorophenyl, a fluorophenyl, 2,6- diethyl phenyls, 2,6- difluorophenyls, o-trifluoromethyl phenyl,
Chloro-O-Phenyl, 3,5- 3,5-dimethylphenyls, 2,4,6- trimethylphenyls, adjacent Trifluoromethoxyphen-l, to ethylphenyl.
2. a kind of system of 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds according to claim 1
Preparation Method, it is characterised in that comprise the following steps that：
1) by difluoro ethyl acetoacetate and triethyl orthoformate in acetic anhydride back flow reaction, reaction terminates rear vacuum distillation and obtains
Compound shown in formula (II), the i.e. fluoro- 3- methyl acetoacetates of (E) -2- ethoxymeyhylenes -4,4- bis-；Then formula (II) institute
The compound shown and methyl hydrazine back flow reaction in ethanol, reaction terminate rear vacuum distillation, extract, obtain the change shown in formula (III)
Compound；
2) compound hydrolysis shown in formula (III) is obtained into the compound shown in formula (IV), i.e. 1- methyl -3- difluoromethyls -1H- pyrroles
Azoles -4- carboxylic acids；Compound and thionyl chloride back flow reaction shown in formula (IV), reaction terminate rear vacuum distillation and obtained shown in formula (V)
Compound, i.e. 1- methyl -3- difluoromethyls -1H- pyrazoles -4- acyl chlorides；
3) compound shown in formula (V) is added in organic solvent, is then added dropwise in 25% ammoniacal liquor, reacted at room temperature,
Obtain the compound shown in compound formula (VI), i.e. 1- methyl -3- difluoromethyls -1H- pyrazoles -4- acid amides；By shown in formula (VI)
Compound is added in oxalyl chloride, is stirred at room temperature rear back flow reaction, and reaction terminates rear vacuum distillation and obtains chemical combination shown in formula (VII)
Thing；
4) anil of the different substituents shown in formula (VIII) is added to the organic molten of the compound shown in formula (VII)
In agent, reaction overnight, reaction terminates rear vacuum distillation, recrystallizes to obtain target compound shown in formula (I)；
In formula (VIII), X is monosubstituted or polysubstituted fluorine atom, chlorine atom, trifluoromethyl, trifluoromethoxy, methyl or second
Base.
3. a kind of system of 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds according to claim 2
Preparation Method, it is characterised in that step 1) in difluoro ethyl acetoacetate, triethyl orthoformate and acetic anhydride the ratio between the amount of material
For 1:1.0~2.0:The ratio between amount of material of compound and methyl hydrazine shown in 2.0~3.0. formulas (II) is 1:1.5~2.0, second
The volumetric usage of alcohol is calculated as 0.5~1.0ml/mmol with the amount of the material of formula (II) compound.
4. a kind of system of 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds according to claim 2
Preparation Method, it is characterised in that step 2) in alkali used in compound hydrolysis shown in formula (III) be potassium hydroxide or sodium hydroxide, alkali
Concentration be 4%~6%, the ratio between amount of material of compound and thionyl chloride shown in formula (IV) be 1:8~15.
5. a kind of system of 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds according to claim 2
Preparation Method, it is characterised in that step 3) in organic solvent be dichloromethane or chloroform, organic solvent volume consumption is with formula
(V) amount of the material of the compound shown in is calculated as 0.5~1.0ml/mmol.
6. a kind of system of 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds according to claim 2
Preparation Method, it is characterised in that step 3) in the ratio between compound shown in formula (VI) and the amount of material of oxalyl chloride be 1:8~12.
7. a kind of system of 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds according to claim 2
Preparation Method, it is characterised in that step 4) in organic solvent be dichloromethane, chloroform, acetone or tetrahydrofuran in one kind
Or it is a variety of；With formula, (amount of the material of the compound shown in (VII) is calculated as 0.1~0.3ml/mmol to organic solvent volume consumption.
8. a kind of system of 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds according to claim 2
Preparation Method, it is characterised in that step 4) in compound and the amount of the material of the compound shown in formula (VIII) shown in formula (VII)
The ratio between be 1:1.0~1.5.
9. a kind of system of 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamide carbamide compounds according to claim 2
Preparation Method, it is characterised in that step 4) in the used solvent of recrystallization be ethanol, ethyl acetate, petroleum ether, one kind in chloroform
Or several mixtures.
10. a kind of 1- methyl -3- difluoromethyls -1H- pyrazole-4-carboxamides carbamide compounds as claimed in claim 1 are in system
Application in standby preventing and treating Cucumber Target Leaf Spot, cucumber bacterium angular leaf spot, botrytis cinerea pers, cucumber fusarium axysporum bactericide.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109320451A (en) * | 2018-11-20 | 2019-02-12 | 浙江树人学院 | Fluorine-containing cigarette acyl urea compound and preparation method and application |
| CN109369533A (en) * | 2018-12-26 | 2019-02-22 | 浙江本立科技股份有限公司 | The preparation method of 3- difluoromethyl -1- methvl-pyridinium -4- dicarbonyl chloride |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06157469A (en) * | 1992-11-13 | 1994-06-03 | Ube Ind Ltd | Pyrazole-carbonylurea derivative its production and pest-controlling agent |
| CN102838535A (en) * | 2012-09-14 | 2012-12-26 | 浙江工业大学 | Preparation method of nicotinoyl thiourea derivatives |
-
2017
- 2017-04-30 CN CN201710298170.6A patent/CN107033081A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06157469A (en) * | 1992-11-13 | 1994-06-03 | Ube Ind Ltd | Pyrazole-carbonylurea derivative its production and pest-controlling agent |
| CN102838535A (en) * | 2012-09-14 | 2012-12-26 | 浙江工业大学 | Preparation method of nicotinoyl thiourea derivatives |
Non-Patent Citations (3)
| Title |
|---|
| 刘长令 等: "新型吡唑甲酰脲类化合物的合成及其生物活性", 《化学研究与应用》 * |
| 刘长令 等: "新型吡唑甲酰脲类化合物的合成及其生物活性", 《合成化学》 * |
| 孙娜波 等: "新型吡唑酰基脲类化合物的设计合成、杀菌活性与分子对接研究", 《有机化学》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109320451A (en) * | 2018-11-20 | 2019-02-12 | 浙江树人学院 | Fluorine-containing cigarette acyl urea compound and preparation method and application |
| CN109369533A (en) * | 2018-12-26 | 2019-02-22 | 浙江本立科技股份有限公司 | The preparation method of 3- difluoromethyl -1- methvl-pyridinium -4- dicarbonyl chloride |
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