Trifluoromethyl pyridine amide-containing compound, preparation method and application thereof, and bactericide
阅读说明：本技术 含三氟甲基吡啶酰胺类化合物及其制备方法和应用以及杀菌剂 (Trifluoromethyl pyridine amide-containing compound, preparation method and application thereof, and bactericide ) 是由 杨光富 李华 于 2019-07-26 设计创作，主要内容包括：本发明涉及农药杀菌剂领域,公开了一种含三氟甲基吡啶酰胺类化合物及其制备方法和应用以及杀菌剂,该含三氟甲基吡啶酰胺化合物具有式(1)所示的结构,本发明通过引入含三氟甲基吡啶结构和二苯醚片段,设计出了具有广泛活性的含三氟甲基吡啶酰胺类化合物,该含三氟甲基吡啶酰胺类化合物能够作为全新的琥珀酸脱氢酶抑制剂或杀菌剂。<Image he="335" wi="700" file="DDA0002145165200000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention relates to the field of pesticide bactericides and discloses a compound containing trifluoromethyl pyridine amide, a preparation method and application thereof as well as a bactericide, wherein the compound containing trifluoromethyl pyridine amide has a structure shown in a formula (1).)
1. A compound containing trifluoromethyl pyridine amide, which has a structure shown as a formula (1):
wherein R is 11Selected from halogen, C substituted by 1-9 halogens 1-4Alkyl group of (1).
2. The compound according to claim 1, wherein R is represented by formula (1) 11Selected from fluorine, chlorine, bromine, iodine, -CF 3、-CHF 2、-CH 2F、-CH 2CF 3、-CH 2CH 2CF 3、-C(CF 3) 3(ii) a Preferably, the first and second electrodes are formed of a metal,
the structure of the compound shown in the formula (1) is at least one of the following structures:
3. a process for preparing a compound of claim 1 or 2 comprising trifluoromethylpicolinamide, which comprises: carrying out contact reaction on a compound shown as a formula (2-1) and a compound shown as a formula (2-2),
wherein R is 11Are correspondingly the same as defined in claim 1 or 2.
4. The method according to claim 3, wherein the contact reaction between the compound represented by the formula (2-1) and the compound represented by the formula (2-2) is carried out under conditions comprising: the temperature is 0-100 ℃ and the time is 1-48 h.
5. Use of the compound of claim 1 or 2 as succinate dehydrogenase inhibitor.
6. Use of the compound containing trifluoromethylpyridine amides according to claim 1 or 2 for controlling plant fungal diseases.
7. The use of claim 6, wherein the plant fungus comprises at least one of anthracnose, leaf spot, rust, powdery mildew, sheath blight, leaf blight, gray mold, southern blight, damping off, head blight, take all, and target spot.
8. A bactericide which is composed of an active ingredient and an auxiliary material, wherein the active ingredient comprises at least one of the trifluoromethyl picolinamide compound as defined in claim 1 or 2.
9. The bactericide according to claim 8, wherein the content of the trifluoromethylpicolinamide-containing compound in the bactericide is 1 to 99.9% by weight.
10. The bactericide according to claim 9, wherein the bactericide is in a form selected from at least one of emulsifiable concentrate, suspension, wettable powder, dust, granule, aqueous solution, poison bait, mother liquor and mother powder.
Technical Field
The invention relates to the field of pesticide bactericides, and in particular relates to a compound containing trifluoromethyl picolinamide, a preparation method and application thereof, and a bactericide.
Background
The succinate dehydrogenase inhibitor bactericide has the characteristics of high efficiency, broad-spectrum bactericidal activity and environmental friendliness, has become the bactericide with the greatest development prospect in recent years, and is concerned by various pesticide companies in the world.
The current commercial classes of bactericides as succinate dehydrogenase inhibitors mainly include: pyrazole amides, pyrazine amides, benzamide, methylfuroamide, oxathiolane amides, thiazole amides, pyridine amides. Boscalid, the first broad-spectrum succinate dehydrogenase inhibitor marketed by basf in 2003, was active against almost all types of fungal diseases, was very effective against powdery mildew, gray mold, sclerotinia, various rot diseases, etc., and rapidly became a billion dollar product, the acid moiety of which was 2-chloropyridine.
CN1226244A discloses the use of carbanilide as herbicide and pesticide, specifically discloses the use in plasmodiophora, oomycetes, chytrid, zygomycotina, ascomycetes, basidiomycetes and deuteromycetes, but does not specifically disclose that the compound containing trifluoromethyl picolinamide has obvious succinic dehydrogenase inhibitory activity and has certain inhibitory activity on soybean rust, corn rust, wheat powdery mildew, melon powdery mildew, rice sheath blight, wheat sharp eyespot, strawberry gray mold, peanut southern blight, cotton rhizoctonia solani, wheat scab, wheat take-all and cucumber target spot.
It is well known that pyridine rings have a very broad range of biological activities, with very successful examples in weeding, killing bacteria, killing insects, etc. Often the same pyridine ring substitutes for different groups and has completely different biological activities. Therefore, the design and synthesis of a brand new pyridine compound as a brand new succinate dehydrogenase inhibitor by utilizing the biological activity of the pyridine ring becomes an effective method.
Disclosure of Invention
One of the purposes of the invention is to provide a compound containing trifluoromethyl pyridine amide, which has broad-spectrum bacteriostatic and bactericidal activity.
The invention also aims to provide a compound containing trifluoromethyl pyridine amide which can be used as a succinate dehydrogenase inhibitor.
The invention also aims to provide a compound containing trifluoromethyl pyridine amide which can be used as a main active ingredient of a bactericide.
The inventor of the present invention found in research that when the ortho position of N on the pyridine ring of the compound represented by formula (1) in the present application is trifluoromethyl, and the para position of the ether bond structure on the "free" benzene ring in the diphenyl ether structure of the compound represented by formula (1) is trifluoromethyl and the ortho position is halogen or halogen-substituted alkyl, the compound has significant succinate dehydrogenase inhibitory activity and has certain inhibitory activity on soybean rust, corn rust, wheat powdery mildew, melon powdery mildew, rice sheath blight, wheat sharp eyespot, strawberry gray mold, peanut southern blight, cotton blight, wheat scab, wheat take all and cucumber target spot. Particularly, the compound containing trifluoromethyl pyridine amide provided by the invention has higher control effect on wheat powdery mildew, soybean rust disease, corn rust disease, rice sheath blight disease and cucumber powdery mildew than boscalid and pyraziflumumid (NNF-0721), and has obviously better control effect on plant fungal diseases at extremely low concentration than the compounds in the prior art such as boscalid and pyraziflumumid (NNF-0721).
In order to achieve the above object, in a first aspect, the present invention provides a trifluoromethyl pyridine amide-containing compound having a structure represented by formula (1):
wherein R is 11Selected from halogen, C substituted by 1-9 halogens 1-4Alkyl group of (1).
In a second aspect, the present invention provides a process for preparing a trifluoromethylpyridine amide-containing compound according to the present invention, which comprises: carrying out contact reaction on a compound shown as a formula (2-1) and a compound shown as a formula (2-2),
wherein R is 11Selected from halogen, C substituted by 1-9 halogens 1-4Alkyl group of (1).
In a third aspect, the invention provides an application of the trifluoromethyl pyridine amide-containing compound as a succinate dehydrogenase inhibitor.
In a fourth aspect, the invention provides an application of the compound containing trifluoromethyl pyridine amide in resisting plant fungal diseases.
In a fifth aspect, the invention provides a bactericide, which is composed of an active ingredient and an auxiliary material, wherein the active ingredient comprises at least one of the trifluoromethyl pyridine amide-containing compounds disclosed by the invention.
The compound containing trifluoromethyl pyridine amide provided by the invention has certain inhibitory activity on succinate dehydrogenase, soybean rust, corn rust, wheat powdery mildew, melon powdery mildew, rice sheath blight, wheat sheath blight, strawberry gray mold, peanut southern blight, cotton rhizoctonia rot, wheat scab, wheat take-all and cucumber target spot. The control effect of the compound containing trifluoromethyl pyridine amide provided by the invention on wheat powdery mildew, soybean rust, corn rust, rice sheath blight and cucumber powdery mildew is higher than that of a comparative compound boscalid and a comparative compound pyraziflumumid (NNF-0721), wherein the structures of the boscalid and the pyraziflumumid (NNF-0721) are as follows:
meanwhile, the method for preparing the pyridine amine compound has the advantages of cheap and easily-obtained raw materials, mild reaction conditions and simple post-treatment.
Moreover, the invention proves that the trifluoromethyl pyridine amide-containing compound has good bactericidal activity through the data in the specific examples.
Detailed Description
The following describes in detail specific embodiments of the present invention. The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.
According to the invention First aspectThe invention provides a trifluoromethyl pyridine amide-containing compound, which has a structure shown in a formula (1):
wherein R is 11Selected from halogen, C substituted by 1-9 halogens 1-4Alkyl group of (1).
In the present invention, "C substituted by 1 to 9 halogens 1-4The "alkyl group" of (a) represents an alkyl group having 1 to 4 carbon atoms, and 1 to 9H atoms of the alkyl group are substituted with halogen, and for example, 1 to 9H atoms of methyl, ethyl, n-propyl, isopropyl, n-butyl and tert-butyl groups may be substituted with halogen.
The halogen of the present invention includes fluorine, chlorine, bromine and iodine.
Preferably, in the present invention, in the structure represented by formula (1), R is 11Selected from fluorine, chlorine, bromine, iodine, -CF 3、-CHF 2、-CH 2F、-CH 2CF 3、-CH 2CH 2CF 3、-C(CF 3) 3。
Preferably, the structure of the compound represented by the formula (1) is at least one of the following:
in the present invention, the person skilled in the art can obtain the compound represented by formula (1) of the present invention by combining a conventional synthetic method in the field of organic chemistry according to the specific structure of the compound represented by formula (1).
In the present invention, for the purpose of achieving a higher yield of the objective compound, the present invention provides a preferred embodiment for preparing the compound represented by the aforementioned formula (1), specifically, as in the present invention Second aspect of the inventionThe method for preparing the compound containing the trifluoromethyl pyridine amide is characterized in that the compound shown as the formula (2-1) and the compound shown as the formula (2-2) are subjected to contact reaction,
wherein R is 11Are correspondingly the same as defined above for the compounds of the invention.
According to the present invention, it is preferred that the contact reaction comprises conducting in the presence of a catalyst and a first organic solvent.
Preferably, the conditions of the contact reaction include: the compound shown in the formula (2-1), the catalyst and the compound shown in the formula (2-2) are used in a molar ratio of 1: (1.25-5): (0.6-1.5), more preferably 1: (1.25-2.5): (0.8-1.2).
Preferably, the conditions for the contact reaction of the compound represented by the formula (2-1) with the compound represented by the formula (2-2) include: the temperature is 0-100 ℃, and more preferably 20-50 ℃; the time is 1-48h, more preferably 1-18 h.
In the present invention, examples of the catalyst preferably include at least one of 2- (7-azobenzotriazol) -N, N' -tetramethyluronium hexafluorophosphate, N-diisopropylethylamine, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 1-hydroxybenzotriazole, and more preferably a combination of both catalysts. For example, when 2- (7-azobenzotriazol) -N, N, N ', N' -tetramethylurea hexafluorophosphate and N, N-diisopropylethylamine are combined, the molar ratio of the 2- (7-azobenzotriazol) -N, N, N ', N' -tetramethylurea hexafluorophosphate to the N, N-diisopropylethylamine is 1 (0.5-2).
In the present invention, the first organic solvent includes, for example, dichloromethane, and the amount of the first organic solvent is not particularly limited as long as the reaction requirements can be satisfied.
In the present invention, the source of the compound represented by the formula (2-1) and the compound represented by the formula (2-2) is not particularly limited, and may be, for example, commercially available, or may be designed and synthesized by selecting a synthetic method which is conventional in the art according to a substituent.
According to the present invention, preferably, the compound represented by the formula (2-2) is an intermediate, and the method further comprises preparing the compound represented by the formula (2-2) by:
in the presence of a second organic solvent and a basic compound, carrying out first contact on the compound shown in the formula (2-3) and o-aminophenol to obtain a compound shown in the formula (2-2),
wherein R is 11Are correspondingly the same as defined above for the compounds of the invention.
According to the present invention, it is preferable that the compound represented by the formula (2-3), the basic compound and the o-aminophenol are used in the first contact in a molar ratio of 1: (1-5): (1-4), more preferably 1: (1-2): (1-2);
preferably, the conditions of the first contacting include: the temperature is 30-150 deg.C, preferably 60-100 deg.C, and the time is 1-24 hr, preferably 1-10 hr.
In the present invention, examples of the basic compound preferably include one of anhydrous potassium carbonate, sodium hydroxide, potassium hydroxide, and calcium hydroxide.
In the present invention, examples of the second organic solvent include at least one of N, N-dimethylformamide, dimethylsulfoxide and N, N-dimethylacetamide, and the specific amount of the second organic solvent is not limited as long as reaction conditions can be satisfied.
In the present invention, the preparation method of the compound represented by formula (1) is as described above, and specifically comprises the following reaction formula:
reaction type 1
According to the invention Third aspect of the inventionThe invention provides application of the trifluoromethyl pyridine amide-containing compound as a succinate dehydrogenase inhibitor.
According to the invention Fourth aspect of the inventionThe invention provides application of the trifluoromethyl pyridine amide-containing compound in resisting plant fungal diseases.
In the invention, the plant fungi comprise at least one of anthracnose, leaf spot, rust disease, powdery mildew, banded sclerotial blight, leaf blight, gray mold, southern blight, damping off, gibberellic disease, take-all and target spot.
In the present invention, examples of the plant having the plant fungal disease include soybean, corn, wheat, melon, rice, wheat, strawberry, peanut, cotton, and examples of the plant fungal disease include soybean rust, corn rust, wheat powdery mildew, melon powdery mildew, rice sheath blight, wheat sharp eyespot, strawberry gray mold, peanut southern blight, cotton rhizoctonia solani, wheat scab, wheat take-all and cucumber target spot, all of which have a certain inhibitory activity, wherein the melon powdery mildew includes, for example, cucumber powdery mildew and the like.
According to the invention Fifth aspect of the inventionThe bactericide is composed of an active ingredient and an auxiliary material, wherein the active ingredient comprises at least one of the trifluoromethyl pyridine amide compounds.
According to the present invention, in the bactericide, the content of the trifluoromethylpicolinamide-containing compound in the bactericide is preferably 1 to 99.9% by weight, more preferably 5 to 95% by weight.
In the invention, the dosage form of the bactericide is at least one selected from missible oil, suspending agent, wettable powder, granules, aqueous solution, poison bait, mother liquor and mother powder.
In the present invention, the adjuvant may be various adjuvants conventionally used in the art, and may be, for example, a surfactant, a solvent, etc.
The present invention will be described in detail below by way of examples.
In the following examples, the various starting materials used are commercially available in chemical purity, unless otherwise specified.
Preparation example 1: for preparing a compound represented by an intermediate formula (2-2)
Adding 3mmol of the compound represented by the formula (2-3), 3.6mmol of 2-aminophenol and 4.5mmol of potassium carbonate into a 50mL round-bottom flask, adding 20mL of N, N-dimethylformamide, heating to 100 ℃, stopping the reaction after TLC monitors that the raw materials react completely, adding 50mL of ethyl acetate, washing with 50mL of saturated common salt twice, adding anhydrous sodium sulfate, drying, removing the solvent under reduced pressure, and carrying out column chromatography to obtain a compound represented by an intermediate (2-2), wherein the structure of the compound represented by the formula (2-2) is shown in Table 1.
TABLE 1
Compound (I)
Case of substituent
I1
R
11Is CF
3
I2
R
11Is Cl
I3
R
11Is Br
I4
R
11Is I