阅读说明：本技术 一种n-取代基苯甲醛缩氨基硫脲类衍生物及其制备方法和应用 (A kind of N- substituent group benzaldehyde thiosemicarbazone analog derivative and its preparation method and application ) 是由 黄洁 张星 齐帆 王思凡 于 2019-08-13 设计创作，主要内容包括：本发明公开了一种N-取代基苯甲醛缩氨基硫脲类衍生物及其制备方法与应用。该衍生物的结构式如下所示：<Image he="213" wi="700" file="DDA0002164613600000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>式中,R<Sub>1</Sub>、R<Sub>2</Sub>各自独立的代表氢原子、卤素、C<Sub>1</Sub>～C<Sub>3</Sub>烷基、C<Sub>1</Sub>～C<Sub>3</Sub>烷氧基、三氟甲基、硝基、羟基或氰基。本发明N-取代基苯甲醛缩氨基硫脲类衍生物的制备方法简单,反应条件温和,产率高,易于工业化生产。本发明N-取代基苯甲醛缩氨基硫脲类衍生物的结构简单,生物活性较好,对植物病原真菌有较好的防治效果,具有强烈的抑制活性,在制备抗植物病原真菌方面具有非常大的价值意义。(The invention discloses a kind of N- substituent group benzaldehyde thiosemicarbazone analog derivatives and the preparation method and application thereof.The structural formula of the derivative is as follows: In formula, R 1 、R 2 It is independent to represent hydrogen atom, halogen, C 1 ~C 3 Alkyl, C 1 ~C 3 Alkoxy, trifluoromethyl, nitro, hydroxyl or cyano.The preparation method of N- substituent group benzaldehyde thiosemicarbazone analog derivative of the present invention is simple, and reaction condition is mild, and yield is high, easy to industrialized production.The structure of N- substituent group benzaldehyde thiosemicarbazone analog derivative of the present invention is simple, and bioactivity is preferable, has preferable control efficiency to plant pathogenic fungi, has strong inhibitory activity, has very big significance in terms of preparing anti-plant pathogenic fungi.)

1. a kind of N- substituent group benzaldehyde thiosemicarbazone analog derivative, it is characterised in that the following institute of the structural formula of the derivative Show:

In formula, R₁、R₂It is independent to represent hydrogen atom, halogen, C₁~C₃Alkyl, C₁~C₃Alkoxy, trifluoromethyl, nitro, Any one in hydroxyl, cyano.

2. N- substituent group benzaldehyde thiosemicarbazone analog derivative according to claim 1, it is characterised in that the derivative For any one in following compounds 1~6:

3. a kind of preparation method of N- substituent group benzaldehyde thiosemicarbazone analog derivative described in claim 1, feature exist In:

(1) 4- ethyl aniline is dissolved in the ethanol water that volumetric concentration is 85%~95%, and mass concentration is added and is 25%~28% ammonium hydroxide and carbon disulfide normal-temperature reaction 1~2 hour, adds sodium chloroacetate, continues to be stirred to react 1~1.5 Hour, the hydrazine hydrate aqueous solution that volumetric concentration is 60%~85% is then added dropwise, return stirring is reacted 2~3 hours, obtained N- described in Formulas I (4- ethylphenyl) thiosemicarbazides；

(2) N- (4- ethylphenyl) thiosemicarbazides is dissolved in the ethanol water that volumetric concentration is 85%~95%, then Compound of benzaldehyde category shown in Formula II is added dropwise, 25~40 DEG C are stirred to react 2~4 hours, obtain N- and replace benzaldehyde contracting Thiosemicarbazides analog derivative；

In Formula II, R₁、R₂It is independent to represent hydrogen atom, halogen, C₁~C₃Alkyl, C₁~C₃Alkoxy, trifluoromethyl, nitre Base, hydroxyl, any one in cyano.

4. the preparation method of N- substituent group benzaldehyde thiosemicarbazone analog derivative according to claim 3, feature exist In: in step (1), the molar ratio of the 4- ethyl aniline and ammonia, carbon disulfide is 1:3.5~5:1~1.5.

5. the preparation method of N- substituent group benzaldehyde thiosemicarbazone analog derivative according to claim 3, feature exist In: in step (1), the molar ratio of the 4- ethyl aniline and sodium chloroacetate is 1:1~1.5.

6. the preparation method of N- substituent group benzaldehyde thiosemicarbazone analog derivative according to claim 3, feature exist In: in step (1), the molar ratio of the 4- ethyl aniline and hydrazine hydrate is 1:1~1.5.

7. the preparation method of N- substituent group benzaldehyde thiosemicarbazone analog derivative according to claim 3, feature exist In: in step (2), the molar ratio of N- (4- ethylphenyl) thiosemicarbazides and compound of benzaldehyde category is 1:1~1.5.

8. N- substituent group benzaldehyde thiosemicarbazone analog derivative described in claim 1 is preparing the use in anti-mycotic material On the way.

9. N- substituent group benzaldehyde thiosemicarbazone analog derivative according to claim 8 is preparing anti-plant pathogenic fungi Purposes in material, it is characterised in that: the plant pathogenic fungi be grape hemorrhagic black smallpox bacterium, apple wheel line bacterium, gibberella saubinetii, At least one of potato dry rot fungus.

Technical field

The invention belongs to novel green technical field of medicine synthesis, and in particular to N- substituent group benzaldehyde thiosemicarbazone class Derivative and its preparation method and application.

Background technique

Pesticide has had very long history, and since the mankind begin to use pesticide, a large amount of fungicide, is removed insecticide Careless agent etc. emerges in large numbers, and becomes the great direction of many scholar's researchs, has contributed immense strength for agricultural production.But it is following , also there is pesticide abuse to lead to the problems such as environmental pollution is serious, and single variety makes germ develop drug resistance.Therefore, develop efficiently, The novel environment friendly agricultural of low toxicity, low-residual, mechanism of action is extremely urgent.

The presence of center thiourea group (- HN-CS-NH-) in thiourea derivative is that this kind of compound has good biological Active key.By aldehydes or ketones and the thiosemicarbazone derivatives of thiosemicarbazides building because of itself and macromolecular or metal ion production Raw complex or formation chelate also show good bioactivity, such as in antibacterial, anticancer, weeding, anti-oxidant, treating tuberculosis There is good application prospect with plant growth regulator etc..Saeed A et al. utilizes 1- (aroyl) -3- substituting thioureido Its antibacterial activity is measured in vitro, it is found that such drug has stronger antibacterial living for Gram-negative bacteria and gram-positive bacteria Property, 1- (fluoro benzoyl) -3- (fluorophenyl) thiocarbamide in addition synthesized finds that it is better than antibacterial effect to antimycotic effect Fruit further demonstrates the antibacterial activity that thiourea derivatives are conducive to enhance drug.

Summary of the invention

The object of the present invention is to provide a kind of N- substituent group benzaldehyde thiosemicarbazone analog derivatives, and mention for the derivative For a kind of preparation method and new application.

For above-mentioned purpose, the following institute of the structural formula of N- substituent group thiosemicarbazone derivatives of the present invention Show:

In formula, R₁、R₂It is independent to represent hydrogen atom, halogen, C₁~C₃Alkyl, C₁~C₃Alkoxy, trifluoromethyl, nitre Base, hydroxyl, any one in cyano.

It is any one in the preferably following compounds 1~6 of N- substituent group benzaldehyde thiosemicarbazone analog derivative of the invention Kind:

The preparation method of above-mentioned N- substituent group benzaldehyde thiosemicarbazone analog derivative is made of following step:

1,4- ethyl aniline is dissolved in the ethanol water that volumetric concentration is 85%~95%, and mass concentration is added For 25%~28% ammonium hydroxide and carbon disulfide, normal-temperature reaction 1~2 hour, sodium chloroacetate is added, continue to be stirred to react 1~ 1.5 hours, the hydrazine hydrate aqueous solution that volumetric concentration is 60%~85% is then added dropwise, return stirring reacts 2~3 hours, Obtain N- described in Formulas I (4- ethylphenyl) thiosemicarbazides.

2, N- (4- ethylphenyl) thiosemicarbazides is dissolved in the ethanol water that volumetric concentration is 85%~95%, so After compound of benzaldehyde category shown in Formula II is added dropwise, 25~40 DEG C are stirred to react 2~4 hours, obtain N- replace benzaldehyde Thiosemicarbazone derivatives.

In above-mentioned steps 1, preferably 4- ethyl aniline and the molar ratio of ammonia, carbon disulfide is 1:3.5~5:1~1.5,4- second The molar ratio of base aniline and sodium chloroacetate is 1:1~1.5, and the molar ratio of 4- ethyl aniline and hydrazine hydrate is 1:1~1.5.

In above-mentioned steps 2, the molar ratio of preferably N- (4- ethylphenyl) thiosemicarbazides and compound of benzaldehyde category be 1:1~ 1.5。

Substituent group benzaldehyde thiosemicarbazone analog derivative of the present invention is preparing the purposes in anti-mycotic material, wherein described Plant pathogenic fungi be at least one of grape hemorrhagic black smallpox bacterium, apple wheel line bacterium, gibberella saubinetii, potato dry rot fungus.

Beneficial effects of the present invention are as follows:

1, the structure of N- substituent group thiosemicarbazone derivatives of the present invention is simple, in its structure, different substituent groups Group and specific structure will generate different bioactivity, and the introducing of halogen atom so that the compound fat-soluble enhancing, Be conducive to improve drug effect, there is apparent application prospect in terms of bioactivity.

2, the preparation method of N- substituent group thiosemicarbazone derivatives of the present invention is simple, and reaction condition is mild, and yield is high, It is easy to industrialized production.

3, N- substituent group thiosemicarbazone derivatives bioactivity of the present invention is preferable, has preferably to plant pathogenic fungi Control efficiency has strong inhibitory activity, has very big significance in terms of preparing anti-plant pathogenic fungi.

Detailed description of the invention

Fig. 1 is the crystal structure figure of compound 1 in embodiment 1.

Fig. 2 be compound 1 in embodiment 1 nucleus magnetic hydrogen spectrum (¹H NMR) figure；

Fig. 3 be compound 1 in embodiment 1 nuclear-magnetism carbon spectrum (¹³C NMR) figure；

Specific embodiment

The present invention is described in more detail with reference to the accompanying drawings and examples, but protection scope of the present invention is not limited only to These embodiments.