阅读说明：本技术 一类含磺酰肼结构的4,5-二氢噻唑羧酸类衍生物及其制备方法和应用 (4, 5-dihydrothiazole carboxylic acid derivatives containing sulfonyl hydrazide structure and preparation method and application thereof ) 是由 李凤云 李�根 龚珈苧 李鑫 韩永艳 于 2019-11-07 设计创作，主要内容包括：本发明涉及通式(I)所示的一类具有杀菌活性的一类含磺酰肼结构的4,5-二氢噻唑羧酸类衍生物及其制备方法和应用,将不同取代的天然源化合物的(R)-2-芳基-4,5-二氢噻唑-4-羧酸与苯基磺酰肼进行拼接,其中R1-R10如说明书中所限定。本发明的技术效果是：发现了一类具有广谱杀菌活性的含磺酰肼结构的4,5-二氢噻唑羧酸类衍生物,是一种具有广阔应用前景的生态型杀菌剂。<Image he="315" wi="672" file="DSA0000194236850000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention relates to a 4, 5-dihydrothiazole carboxylic acid derivative containing a sulfonyl hydrazide structure and having bactericidal activity shown in a general formula (I), and a preparation method and application thereof, wherein (R) -2-aryl-4, 5-dihydrothiazole-4-carboxylic acid of different substituted natural source compounds is spliced with phenyl sulfonyl hydrazide, wherein R1-R10 are defined in the specification. The invention has the technical effects that: the 4, 5-dihydrothiazole carboxylic acid derivatives containing the sulfonyl hydrazide structure and having broad-spectrum bactericidal activity are discovered, and are ecological bactericides with wide application prospects.)

1. A4, 5-dihydrothiazole carboxylic acid derivative containing a sulfonyl hydrazide structure is characterized by having the following general formula (I-III):

in the formula:

R₁-R₁₀hydrogen, halogen, nitro, cyano; alkyl, haloalkyl,

In the definition of the above derivatives, the terms used, whether used alone or in compound words, represent the following substituents:

halogen is fluorine, chlorine, bromine or iodine;

alkyl is straight or branched chain alkyl;

haloalkyl groups are straight-chain or branched alkyl groups, the hydrogen atoms on these alkyl groups being able to be substituted partly or completely by halogen atoms.

2. A synthetic method of 4, 5-dihydrothiazole carboxylic acid derivatives containing a sulfonyl hydrazide structure is shown as follows:

the preparation steps are as follows:

the method comprises the following steps: adding the compound 2 into an organic solvent at room temperature, adding a condensing agent at 0 ℃, stirring at 0 ℃ for 0.5h after adding, raising the temperature to room temperature, stirring for 0.5h, then lowering the temperature to 0 ℃, then sequentially adding 1-1.1 equivalent of the compound 1 and 1.2-1.5 equivalent of alkali into a reaction system, slowly raising the temperature to room temperature after adding, monitoring the reaction process by TLC, adding the organic solvent for dilution after the reaction is finished, then sequentially using water, dilute hydrochloric acid, saturated sodium bicarbonate aqueous solution and saturated salt water for washing, removing a water layer, reserving and combining organic phases, adding a drying agent for drying, and then purifying by column chromatography to obtain the compound of the general formula I. The groups in the reaction formula are shown above.

3. The method for preparing 4, 5-dihydrothiazolecarboxylic acid derivatives containing a sulfonyl hydrazide structure as claimed in claim 2, wherein: the organic solvent is dichloromethane, chloroform or tetrahydrofuran.

4. The method for preparing 4, 5-dihydrothiazolecarboxylic acid derivatives containing a sulfonyl hydrazide structure as claimed in claim 2, wherein: the condensing agent is EDCI and HOBt, EDCI and DMAP, DCC and DMAP, HBTU, CDI, PyBOP and HATU.

5. The method for preparing 4, 5-dihydrothiazolecarboxylic acid derivatives containing a sulfonyl hydrazide structure as claimed in claim 2, wherein: the alkali is triethylamine, N-diisopropylethylamine and pyridine.

6. The use of the 4, 5-dihydrothiazolecarboxylic acid derivatives containing a sulfonyl hydrazide structure as claimed in claim 1, wherein: for the preparation of agricultural fungicides based on natural sources, in particular for the control of fungi of plant origin; the pesticide composition can also be used as an active ingredient and matched with agriculturally acceptable auxiliaries to be used for controlling plant-derived fungi.

Technical Field

The invention relates to a synthetic technology of an agricultural bactericide based on a natural source, in particular to a 4, 5-dihydrothiazole carboxylic acid derivative containing a sulfonyl hydrazide structure, a preparation method and application thereof.

Background

The natural product is a huge resource treasury, and the search of the pesticide active compound from the natural resource treasury becomes an important way and a research hotspot for creating new pesticides. However, most natural products cannot fully meet the requirements of pesticides, and structural modification and optimization are required. 4, 5-dihydrothiazole carboxylic acid compounds are natural products with various biological activities such as anti-tumor, antibacterial and antivirus, and have been widely paid attention and researched in the medical field, but the research on the aspect of preventing and controlling agricultural diseases and insect pests is rarely reported. Compared with the traditional chemical synthetic pesticide, the natural pesticide has the following obvious advantages: (1) the natural pesticide is easy to degrade in the environment; (2) has target specificity and is relatively safe to human, livestock and non-target organisms; (3) the action mode is unique, so that the pests are difficult to generate drug resistance; (4) the source is rich.

Based on the above, in order to develop a novel green and efficient ecological bactericide, a class of 4, 5-dihydrothiazolecarboxylic acid derivatives containing a sulfonyl hydrazide structure, which is not reported in documents, is designed and synthesized, and the in vitro antibacterial activity test result shows that the derivatives have high inhibitory activity on common plant-derived fungi.

Disclosure of Invention

The invention aims to provide 4, 5-dihydrothiazole carboxylic acid derivatives containing a sulfonyl hydrazide structure, a preparation method and application thereof, and the compounds can be widely used for preparing agricultural bactericides and are novel ecological bactericides with wide application prospects. The derivatives have high in-vitro antibacterial activity on common plant-derived fungi, and can be used as a bactericide for preventing and treating the plant-derived fungi.

The 4, 5-dihydrothiazolecarboxylic acid derivative containing the sulfonyl hydrazide structure provided by the invention has the following general formula (I):

in the formula:

R₁-R₁₀hydrogen, halogen, nitro, cyano; alkyl, haloalkyl,

In the definition of the above derivatives, the terms used, whether used alone or in compound words, represent the following substituents:

halogen is fluorine, chlorine, bromine or iodine;

alkyl is straight or branched chain alkyl;

haloalkyl groups are straight-chain or branched alkyl groups, the hydrogen atoms on these alkyl groups being able to be substituted partly or completely by halogen atoms.

A synthetic method of 4, 5-dihydrothiazole carboxylic acid derivatives containing a sulfonyl hydrazide structure is shown as follows:

the preparation steps are as follows:

the method comprises the following steps: adding the compound 2 into an organic solvent at room temperature, adding a condensing agent at 0 ℃, stirring at 0 ℃ for 0.5h after adding, raising the temperature to room temperature, stirring for 0.5h, then lowering the temperature to 0 ℃, then sequentially adding 1-1.1 equivalent of the compound 1 and 1.2-1.5 equivalent of alkali into a reaction system, slowly raising the temperature to room temperature after adding, monitoring the reaction process by TLC, adding the organic solvent for dilution after the reaction is finished, then sequentially using water, dilute hydrochloric acid, saturated sodium bicarbonate aqueous solution and saturated salt water for washing, removing a water layer, reserving and combining organic phases, adding a drying agent for drying, and then purifying by column chromatography to obtain the compound of the general formula I. The groups in the reaction formula are shown above.

The organic solvent is dichloromethane, chloroform or tetrahydrofuran.

The condensing agent is EDCI and HOBt, EDCI and DMAP, DCC and DMAP, HBTU, CDI, PyBOP and HATU.

The alkali is triethylamine, N-diisopropylethylamine and pyridine.

The 4, 5-dihydrothiazole carboxylic acid derivatives containing sulfonyl structures are used for preparing novel ecotype bactericides and are particularly used for preventing and treating plant-derived fungi.

The pesticide composition which is prepared by taking the 4, 5-dihydrothiazole carboxylic acid derivative with the sulfonyl structure as an active ingredient and matching with agriculturally acceptable auxiliaries is used for preventing and treating plant-derived fungi.

The invention has the technical effects that: a4, 5-dihydrothiazole carboxylic acid derivative containing a sulfonyl hydrazide structure and having broad-spectrum bactericidal activity is found, can be widely used for preparing novel ecological bactericides, and is a bactericide with a wide application prospect.

Detailed Description

The present invention will be further described with reference to the following examples, which are provided for better understanding of the present invention and the essential features thereof, and therefore should not be construed as limiting the scope of the present invention.