阅读说明：本技术 含噁唑环的吩嗪类化合物及作为农用杀菌剂的用途 (Phenazine compound containing oxazole ring and application of phenazine compound as agricultural bactericide ) 是由 叶永浩 陈议亮 严威 于 2019-10-09 设计创作，主要内容包括：本发明涉及一类含噁唑环的吩嗪类化合物,以及此类化合物作为农用杀菌剂的用途。该类化合物具有有如下通式：<Image he="272" wi="371" file="DSA0000191773020000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>式中R表示氢、卤素、甲基、羟基、氨基、苯基、苯氧基、二氟甲基、三氟甲基、1-6碳烷氧基,以及同时含有2～4个R所代表的取代基。(The invention relates to phenazine compounds containing oxazole rings and application of the compounds as agricultural bactericides, wherein the compounds have the following general formula of , R in the formula represents hydrogen, halogen, methyl, hydroxyl, amino, phenyl, phenoxy, difluoromethyl, trifluoromethyl and 1-6 carbon alkoxy, and the compounds simultaneously contain 2-4 substituents represented by R.)

1. A kind of cyclic phenazine compound containing oxazole, its characteristic is that it has the following general formula:

Wherein R is selected from: hydrogen, halogen, methyl, hydroxyl, amino, phenyl, phenoxy, difluoromethyl, trifluoromethyl, 1-6 carbon alkoxy, and 2-4 substituents represented by R.

2. The compound of formula (la) of claim 1, comprising the following compounds:

3. The use of the phenazine compounds containing an oxazole ring as claimed in claim 1 for controlling agricultural plant diseases.

4. the use as claimed in claim 3, characterized in that the agricultural diseases are rice sheath blight, sclerotinia rot of colza, wheat scab.

5. According to the use of the compounds 3 and 4, the compounds can be processed into missible oil, aqueous emulsion, microemulsion, wettable powder, water dispersible granule, suspending agent and other suitable formulations.

6. The application of the phenazine compound containing oxazole ring in preventing and treating plant diseases as claimed in claim 1 and 2, which is characterized in that the phenazine compound is combined with one or more of commercial bactericides to prepare compound bactericides; the commercial fungicide is selected from azoxystrobin, pyraclostrobin, prothioconazole, mancozeb, epoxiconazole, tebuconazole, prochloraz, boscalid, fluopicolide, metalaxyl, difenoconazole, propiconazole, chlorothalonil, validamycin, carbendazim and cyhalonil.

Technical Field

The invention relates to a phenazine compound containing an oxazole ring and application thereof as a bactericide in plant disease control, belonging to the technical field of agricultural pharmacy.

Background

The natural phenazine compound is a secondary metabolite widely existing in microorganisms such as pseudomonas and streptomyces, and has different physical and chemical properties and multiple biological activities such as antibiosis, nematode resistance, antimalarial resistance, antioxidation, hypertension resistance, cell proliferation inhibition and the like due to different types and positions of functional groups on a phenazine ring. In the agricultural field, the agricultural antibiotic-shenqinmycin which is independently researched and developed in China is a phenazine compound generated by the metabolism of pseudomonas, has been registered as a pesticide at present, and is applied to the control of plant diseases such as gummy stem blight, root rot and the like.

Oxazole ring is a functional group having important biological activity, and various commercial pesticide varieties contain oxazole rings, such as famoxadone (famoxadone), metamifop (metamifop), chlozolinate (chlozolinate) vinclozolin (vinclozolin), and the like, and have been widely used. Thus, the oxazole ring has important value for the research and development of new pesticides.

Based on an active substructure splicing strategy, the invention introduces an oxazole functional group into a phenazine mother nucleus structure for the first time, and adopts a simple, convenient and economic synthesis method to efficiently synthesize a series of phenazine compounds containing oxazole rings with novel structures. Through determination, the compounds have remarkable antibacterial activity and have the potential of being used as a novel agricultural bactericide for development and application.

Disclosure of Invention

The invention aims to provide a synthesis method of a novel phenazine compound containing an oxazole ring and application of the phenazine compound in plant disease control.

The phenazine compound containing oxazole ring provided by the invention has the following structural general formula:

Wherein R is selected from: hydrogen, halogen, methyl, hydroxyl, amino, phenyl, phenoxy, difluoromethyl, trifluoromethyl, 1-6 carbon alkoxy, and 2-4 substituents represented by R. Wherein, the phenyl substituent group comprises phenyl and phenyl substituted by halogen, hydroxyl, amino and 1-6 carbon alkoxy.

The compound related to the invention can be synthesized by the following route and method, and is characterized by comprising the following four steps:

Step 1: adding aniline compound A and 2-bromo-3-nitrobenzoic acid into 2, 3-butanediol, adding CuCl, Cu powder and N-ethylmorpholine, heating at 70 deg.C, stirring for 15 hr, washing the obtained solution with 0.1M ammonia water, and filtering. The resulting solution was slowly poured into 2M HCl to prepare intermediate B.

Step 2: intermediate B and NaBH₄Adding into 2M NaOAnd (4) heating and refluxing the solution in the H for 5H, cooling in an ice bath after the reaction is finished to obtain a sodium salt of the phenazine acid, and acidifying with dilute hydrochloric acid to obtain a phenazine-1-carboxylic acid intermediate C.

And step 3: and under the ice bath condition, dissolving the intermediate C in dichloromethane, dropwise adding oxalyl chloride and N, N-dimethylformamide under the protection of nitrogen, stirring at room temperature for 16h, removing volatile matters in vacuum, dissolving in dichloromethane, cooling to 0 ℃, dropwise adding ammonia water, stirring for half an hour, filtering the reaction product to obtain a solid, drying, and recrystallizing with ethyl acetate to obtain the phenazine-1-formamide intermediate D.

And 4, step 4: heating the mixture of the intermediate D and 1, 3-dichloroacetone at 130 ℃ for 1h, cooling to room temperature, adding water for quenching, extracting the mixture with dichloromethane, drying an organic phase with sodium sulfate, filtering, concentrating under reduced pressure, and carrying out column chromatography to obtain the target compound.

The synthesis of the phenazine compound containing the oxazole ring provided by the invention has the characteristics of simple steps, high yield and easiness in operation.

The invention relates to a phenazine compound containing an oxazole ring, which preferably has the following structure:

The activity of the phenazine compound containing the oxazole ring on plant pathogenic fungi provided by the invention comprises Rhizoctonia solani (Rhizoctonia solani), rice blast (Magnaporthe grisea), wheat gibberellic disease (Fusarium graminearum), wheat holomyces graminis (Gaeumannomyces graminis), wheat Rhizoctonia cerealis (Rhizoctonia cerealis), Sclerotinia sclerotiorum (Sclerotinia sclerotiorum), tomato early blight (Alternaria solani), tomato gray mold (Botryis cinerea), cucumber colletotrichum (Colletochlorum lagenarium), potato late blight (Phytophthora infestans) and pepper mold (Phytophora capsici).

Detailed Description

The process of the present invention will be described below with reference to specific examples, but the present invention is not limited thereto. The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials may be prepared commercially or by conventional methods, unless otherwise specified.