技术领域technical field
本发明涉及一种含甲基苯并吡嗪结构的腙类化合物作为杀菌剂的应用。The invention relates to the application of a hydrazone compound containing a methylbenzopyrazine structure as a bactericide.
背景技术Background technique
杂环结构是合成药物，农药等物质的重要关键因素，这是由于杂环的高效，低毒和可以进行多样化取代的特点所决定的。它已经成为医药，农药的领域的一个研究热点。腙类化合物具有良好的除草、杀虫、杀菌等广泛的生物活性，同时因其分子结构中含有C＝N亚结构，使其具有较强的配位能力和多样的配位形式，可以合成很多高活性的新型化合物，且腙类化合物及其配合物还有良好的抗肿瘤与抗氧化的活性，因此在农药、医药、检测和材料领域均有应用。更是受到了农药研究者的广泛关注，在新农药创制方面研究越来越深入。上世纪50年代已有商品化的品种，杜邦公司在1973年时报道了二苯甲酮腙类衍生物具有良好杀虫活性，尤其对鳞翅目害虫有高效活性；拜耳公司研制的醌肟腙在防治腐霉菌和土壤真菌引起的种子和苗期病害有较好效果；希夫碱和脂肪酰腙类化合物由明显的除草活性，其对阔叶杂草和稗草具有良好活性。Heterocyclic structure is an important key factor for the synthesis of drugs, pesticides and other substances, which is determined by the high efficiency, low toxicity and diversified substitution characteristics of heterocyclic rings. It has become a research hotspot in the field of medicine and pesticide. Hydrazone compounds have a wide range of biological activities such as good herbicidal, insecticidal, and bactericidal properties. At the same time, because of the C=N substructure in their molecular structure, they have strong coordination ability and various coordination forms. New compounds with high activity, and hydrazone compounds and their complexes also have good antitumor and antioxidant activities, so they have applications in the fields of pesticides, medicine, detection and materials. It has been widely concerned by pesticide researchers, and the research on the creation of new pesticides has become more and more in-depth. There were commercial varieties in the 1950s, and DuPont reported in 1973 that benzophenone hydrazone derivatives had good insecticidal activity, especially for lepidopteran pests; the quinone oxime hydrazone developed by Bayer It has a good effect in preventing and controlling the diseases of seeds and seedlings caused by Pythium and soil fungi; Schiff base and fatty acylhydrazone compounds have obvious herbicidal activity, and they have good activity on broad-leaved weeds and barnyard grass.
发明内容SUMMARY OF THE INVENTION
本发明目的是提供一种含甲基苯并吡嗪结构的腙类化合物作为杀菌剂的应用。The object of the present invention is to provide the application of a hydrazone compound containing a methylbenzopyrazine structure as a bactericide.
所述的一种含甲基苯并吡嗪结构的腙类化合物作为杀菌剂的应用，其特征在于含甲基苯并吡嗪结构的腙类化合物的结构式如(I)所示：Described a kind of hydrazone compound containing methylbenzopyrazine structure as the application of bactericide, it is characterized in that the structural formula of the hydrazone compound containing methylbenzopyrazine structure is shown in (I):
其中:R1为3,4,5-三甲氧基苯基，2,4-二氯苯基，3-硝基苯基，2-溴苯基，2-羟基苯基，2-硝基苯基，2-氟苯基，4-溴苯基，4-异丙基苯基，2-甲氧基苯基，3-氯苯基，4-氟苯基，3,4-二甲氧基苯基，4-甲基苯基，2-呋喃苯基，甲基。Wherein: R1 is 3,4,5-trimethoxyphenyl, 2,4-dichlorophenyl, 3-nitrophenyl, 2-bromophenyl, 2-hydroxyphenyl, 2-nitrophenyl base, 2-fluorophenyl, 4-bromophenyl, 4-isopropylphenyl, 2-methoxyphenyl, 3-chlorophenyl, 4-fluorophenyl, 3,4-dimethoxyphenyl Phenyl, 4-methylphenyl, 2-furylphenyl, methyl.
所述的含甲基苯并吡嗪结构的腙类化合物作为防治尖孢炭疽菌、草莓炭疽菌、枸杞炭疽病菌的杀菌剂的应用。The application of the hydrazone compound containing the methyl benzopyrazine structure as a fungicide for preventing and treating anthracnose oxysporum, anthracnose strawberry, and anthracnose lycium barbarum.
所述的应用，其特征在于R1为2-羟基苯基，2-溴苯基，2,4-二氯苯基，3-氯苯基(B10)，2-呋喃苯基，4-异丙基苯基。The application is characterized in that R1 is 2-hydroxyphenyl, 2-bromophenyl, 2,4-dichlorophenyl, 3-chlorophenyl (B10), 2-furanphenyl, 4-isophenyl Propylphenyl.
所述的含甲基苯并吡嗪结构的腙类化合物的制备方法，其特征在于包括如下步骤：The described preparation method of the hydrazone compound containing methylbenzopyrazine structure is characterized in that comprising the steps:
1)在有机溶剂中，Raney Ni的作用下5-甲基邻硝基苯胺和水合肼反应得到如式1所示的化合物5-甲基邻硝基苯胺；1) in organic solvent, under the effect of Raney Ni, 5-methyl o-nitroaniline and hydrazine hydrate react to obtain compound 5-methyl o-nitroaniline as shown in formula 1;
2)在有机溶剂中，将步骤1)得到的5-甲基邻硝基苯胺在乙醇作用下与MBF反应得到如式2所示的化合物7-甲基-2-羟基-3-苯基喹喔啉；2) in an organic solvent, the 5-methyl-o-nitroaniline obtained in step 1) is reacted with MBF under the action of ethanol to obtain the compound 7-methyl-2-hydroxy-3-phenylquinone shown in formula 2 oxaline;
3)将步骤2)得到的7-甲基-2-羟基-3-苯基喹喔啉与三氯氧磷作用反应生成如式3所示的化合物7-甲基-2-氯-3-苯基喹喔啉；3) The 7-methyl-2-hydroxy-3-phenylquinoxaline obtained in step 2) is reacted with phosphorus oxychloride to generate the compound 7-methyl-2-chloro-3- Phenylquinoxaline;
4)将步骤3)得到的7-甲基-2-氯-3-苯基喹喔啉与水合肼作用反应生成如式4所示的化合物(7-甲基-3-苯基喹喔啉-2-基)肼；4) The 7-methyl-2-chloro-3-phenylquinoxaline obtained in step 3) is reacted with hydrazine hydrate to generate the compound shown in formula 4 (7-methyl-3-phenylquinoxaline) -2-yl)hydrazine;
5)在有机溶剂中，将步骤4)得到的(7-甲基-3-苯基喹喔啉-2-基)肼与取代醛类化合物反应生成如式(I)所示的目标腙类化合物；5) In an organic solvent, react (7-methyl-3-phenylquinoxalin-2-yl)hydrazine obtained in step 4) with a substituted aldehyde compound to generate the target hydrazone shown in formula (I) compound;
制备过程如下：The preparation process is as follows:
所述的含甲基苯并吡嗪结构的腙类化合物的制备方法，其特征在于步骤1)中5-甲基邻硝基苯胺的物质的量和Raney Ni的质量之比为1:2.5～4.5，有机溶剂为甲醇，其体积用量以5-甲基邻硝基苯胺的物质的量计为0.3～0.5ml/mmol，85％的水合肼的用量以5-甲基邻硝基苯胺的物质的量计为0.7～0.8ml/mmol。The preparation method of the described hydrazone compound containing methylbenzopyrazine structure is characterized in that the ratio of the amount of substance of 5-methyl-o-nitroaniline and the mass of Raney Ni in step 1) is 1:2.5～ 4.5, the organic solvent is methanol, and its volumetric consumption is calculated as 0.3～0.5ml/mmol with the material amount of 5-methyl-o-nitroaniline, and the consumption of 85% hydrazine hydrate is with the material of 5-methyl-o-nitroaniline The amount is calculated as 0.7 to 0.8 ml/mmol.
所述的含甲基苯并吡嗪结构的腙类化合物的制备方法，其特征在于步骤2)中4-甲基邻苯二胺与MBF的物质的量之比为1:1.5～3.5。The method for preparing a hydrazone compound containing a methylbenzopyrazine structure is characterized in that in step 2), the ratio of the amount of 4-methyl-o-phenylenediamine to MBF is 1:1.5-3.5.
所述的含甲基苯并吡嗪结构的腙类化合物的制备方法，其特征在于步骤2)中有机溶剂为甲醇、乙醇或DMF，其体积用量以4-甲基邻苯二胺的物质的量计为0.9～1.1ml/mmol。The described preparation method of the hydrazone compound containing methylbenzopyrazine structure is characterized in that in step 2), the organic solvent is methanol, ethanol or DMF, and its volumetric consumption is based on the material of 4-methylo-phenylenediamine. The amount is 0.9 to 1.1 ml/mmol.
所述的含甲基苯并吡嗪结构的腙类化合物的制备方法，其特征在于步骤3)中三氯氧磷体积用量以7-甲基-2-羟基-3-苯基喹喔啉的物质的量计为0.3～0.5ml/mmol。The described preparation method of the hydrazone compound containing methyl benzopyrazine structure is characterized in that in step 3), the volumetric dosage of phosphorus oxychloride is the amount of 7-methyl-2-hydroxy-3-phenylquinoxaline. The amount of the substance is calculated to be 0.3 to 0.5 ml/mmol.
所述的含甲基苯并吡嗪结构的腙类化合物的制备方法，其特征在于步骤4)中7-甲基-2-氯-3-苯基喹喔啉与水合肼的物质的量之比为1:1.5～4.5。The described preparation method of the hydrazone compound containing methylbenzopyrazine structure is characterized in that in step 4), the amount of 7-methyl-2-chloro-3-phenylquinoxaline and hydrazine hydrate is equal to the amount of the substance. The ratio is 1:1.5～4.5.
所述的含甲基苯并吡嗪结构的腙类化合物的制备方法，其特征在于步骤5)中(7-甲基-3-苯基喹喔啉-2-基)肼与取代醛类化合物的物质的量之比为1:0.9～1.1。The preparation method of the hydrazone compound containing methylbenzopyrazine structure is characterized in that in step 5) (7-methyl-3-phenylquinoxalin-2-yl)hydrazine and substituted aldehyde compound The ratio of the amount of the substances is 1:0.9～1.1.
所述的含甲基苯并吡嗪结构的腙类化合物的制备方法，其特征在于步骤5)中有机溶剂为甲醇、乙醇或DMF，其用量以取代醛类化合物的物质的量计为7.0～8.0ml/mmol。The preparation method of the hydrazone compound containing methylbenzopyrazine structure is characterized in that in step 5), the organic solvent is methanol, ethanol or DMF, and its consumption is calculated as 7.0～7. 8.0ml/mmol.
与现有技术相比，本发明的有益效果主要体现在：本发明提供了一种含苯并吡嗪结构的腙类化合物的制备方法以及应用，其原料简单易得，制备方法简单、后处理方便，产品收率高，该化合物为具有抗菌活性，特别是在防治尖孢炭疽菌,草莓炭疽菌,枸杞炭疽病菌具有良好的防治作用，为新农药的研发提供了基础。Compared with the prior art, the beneficial effects of the present invention are mainly reflected in: the present invention provides a preparation method and application of a hydrazone compound containing a benzopyrazine structure, the raw materials are simple and easy to obtain, the preparation method is simple, and the post-processing It is convenient and has high product yield. The compound has antibacterial activity, especially in the control of anthracnose oxysporum, anthracnose of strawberry, and anthracnose of wolfberry, which provides a basis for the research and development of new pesticides.
具体实施方式Detailed ways
下面结合具体实施例对本发明进行进一步描述，但本发明的保护范围并不仅限于此：The present invention is further described below in conjunction with specific embodiment, but the protection scope of the present invention is not limited to this:
本发明的含甲基苯并吡嗪结构的腙类化合物(I)可以如下方法合成：The hydrazone compound (I) containing methylbenzopyrazine structure of the present invention can be synthesized as follows:
下面结合具体实施例对本发明进行进一步描述，但本发明的保护范围并不仅限于此：The present invention is further described below in conjunction with specific embodiment, but the protection scope of the present invention is not limited to this:
本发明的含苯并吡嗪结构的腙类化合物(I)可以如下方法合成：The hydrazone compound (I) containing benzopyrazine structure of the present invention can be synthesized as follows:
在250mL单口烧瓶中，依次加入0.1mol 4-甲基邻硝基苯胺、40mL甲醇、75mL水合肼(85％)、0.25～0.45Rany Ni(湿重)，加热回流，用TCL追踪至原料消失，反应结束后冷却至室温，过滤除去Rany Ni，减压蒸馏除去溶剂得到淡褐色晶体，即得到如式1所示的化合物14-甲基邻苯二胺。在250mL单口烧瓶中，加入0.1mol取代邻苯二胺、用100mL乙醇将其溶解，再缓慢滴加MBF，在滴加过程中有黄色固体出现，根据取代基R1的变化，反应时间不同，在常温下反应时间段为30-120min，反应完全后，过滤除去溶剂，用乙醇冲洗三次，得到如式2所示的化合物7-甲基-2-羟基-3-苯基喹喔啉。在化合物2中加入40mLPOCl3做溶剂，加热回流条件下进行氯化，用TLC追踪至原料消失，反应结束后冷却至室温，缓慢倒入500g冰水中，立即析出大量黄色固体，抽滤、洗涤干燥，得到如式3所示的化合物3。在250mL三口烧瓶中，加入化合物3并用60mL乙醇做溶剂，缓慢滴加18g(0.3mol)85％的水合肼，滴加完毕后升温至回流，反应4-5h，反应结束后冷却至室温，倒入300g冰水中，立即析出大量白色固体，经抽滤、洗涤和干燥，制得粗产品，通过重结晶得如式4所示化合物4。在50mL圆底烧瓶中加入0.377g(0.002mol)肼，加入15mL乙醇做溶剂，搅拌条件下缓慢滴加0.002mol取代醛类化合物，原料迅速溶解，继而有固体析出，室温下搅拌过夜，点板监测，原料反应完全后，抽滤、用石油醚和乙醇的混合液洗涤三次，得红黄色固体粉末，即如式(I)所示的含苯并吡嗪结构的腙类化合物。In a 250mL single-necked flask, sequentially add 0.1mol 4-methyl-o-nitroaniline, 40mL methanol, 75mL hydrazine hydrate (85%), 0.25-0.45Rany Ni (wet weight), heat to reflux, trace with TCL until the raw materials disappear, After the reaction is completed, it is cooled to room temperature, the Rany Ni is removed by filtration, and the solvent is distilled off under reduced pressure to obtain light brown crystals, that is, the compound 14-methyl-o-phenylenediamine shown in formula 1 is obtained. In a 250mL single-necked flask, add 0.1mol of substituted o-phenylenediamine, dissolve it with 100mL of ethanol, and slowly add MBF dropwise, a yellow solid appears during the dropwise addition, and the reaction time is different according to the change of the substituent R1 , The reaction time at room temperature is 30-120 min. After the reaction is complete, the solvent is removed by filtration, and washed with ethanol three times to obtain the compound 7-methyl-2-hydroxy-3-phenylquinoxaline shown in formula 2. 40mL POCl was added to compound2 as solvent, chlorinated under heating and refluxing conditions, followed by TLC until the raw material disappeared, cooled to room temperature after the reaction was completed, slowly poured into 500g ice water, immediately precipitated a large amount of yellow solids, suction filtration, washing and drying , compound 3 shown in formula 3 is obtained. In a 250 mL three-necked flask, compound 3 was added and 60 mL of ethanol was used as a solvent, and 18 g (0.3 mol) of 85% hydrazine hydrate was slowly added dropwise. Pour into 300 g of ice water, and immediately precipitate a large amount of white solids. After suction filtration, washing and drying, a crude product is obtained, and compound 4 shown in formula 4 is obtained by recrystallization. Add 0.377g (0.002mol) of hydrazine to a 50mL round-bottomed flask, add 15mL of ethanol as a solvent, slowly add 0.002mol of substituted aldehydes dropwise under stirring conditions, the raw materials are rapidly dissolved, followed by solid precipitation, stir overnight at room temperature, and spot plate Monitoring, after the reaction of the raw materials is completed, suction filtration, and washing with a mixture of petroleum ether and ethanol three times to obtain a red-yellow solid powder, that is, a hydrazone compound containing a benzopyrazine structure as shown in formula (I).
实施例1～15，具体化合物的结构式如表2所示，其它合成条件不改变。In Examples 1 to 15, the structural formulas of the specific compounds are shown in Table 2, and other synthesis conditions remain unchanged.
实施例1Example 1
(E)-(2-(2-(7-甲基-3-苯基喹喔啉-2-基)肼)甲基)苯酚，红黄色固体，产率87.5％，m.p.113-116℃；1H NMR(400MHz,CDCl3/TMS),δ2.50(S,3H,CH3),6.95(m,1H,Ph-H),7.13(m,1H,Ph-H),7.32-7.88(m,9H,Ph-H),8.10(s,1H,Ph-H),8.29(s,1H,NH),8.70(m,1H,＝CH),11.65(m,1H,OH).HRMS(ESI)m/z:Calculated,355.1553,Found,355.1572[M+H]+(E)-(2-(2-(7-methyl-3-phenylquinoxalin-2-yl)hydrazine)methyl)phenol, red-yellow solid, yield 87.5%, mp113-116°C;1 H NMR (400MHz, CDCl3 /TMS), δ 2.50 (S, 3H, CH3 ), 6.95 (m, 1H, Ph-H), 7.13 (m, 1H, Ph-H), 7.32-7.88 (m ,9H,Ph-H),8.10(s,1H,Ph-H),8.29(s,1H,NH),8.70(m,1H,=CH),11.65(m,1H,OH).HRMS(ESI )m/z: Calculated,355.1553,Found,355.1572[M+H]+
实施例2Example 2
(E)-3-(2-(2-溴苯基)肼)-6-甲基-2-苯基喹喔啉，红黄色固体，产率68.3％，m.p.80-83℃；1H NMR(400MHz,CDCl3/TMS),δ2.52(S,3H,CH3),7.26(q,J＝6.0Hz,1H,Ph-H),7.38(t,J＝6.0Hz,2H,Ph-H),7.57-7.77(m,8H,Ph-H),8.17(m,1H,Ph-H).FTIRυ(cm-1):687.47,1088.49,1462.76,1610.96,2929.38,2958.79,3063.75.HRMS(ESI)m/z:Calculated,417.0709,Found,417.0729[M+H]+(E)-3-(2-(2-Bromophenyl)hydrazine)-6-methyl-2-phenylquinoxaline, red-yellow solid, yield 68.3%, mp80-83°C;1 H NMR ( 400MHz, CDCl3 /TMS), δ 2.52 (S, 3H, CH3 ), 7.26 (q, J=6.0Hz, 1H, Ph-H), 7.38 (t, J=6.0Hz, 2H, Ph-H ),7.57-7.77(m,8H,Ph-H),8.17(m,1H,Ph-H).FTIRυ(cm-1 ):687.47,1088.49,1462.76,1610.96,2929.38,2958.79,3063.75.HRMS(ESI )m/z: Calculated,417.0709,Found,417.0729[M+H]+
实施例3Example 3
(E)-6-甲基-3-(2-(3-硝基苯基)肼)-2-苯基喹喔啉，红黄色固体，产率71.9％，m.p.172-175℃；1H NMR(400MHz,CDCl3/TMS),δ2.55(S,3H,CH3),7.23(d,J＝6.8Hz,1H,Ph-H),7.37(d,J＝6.8Hz,1H,Ph-H),7.63(m,3H,Ph-H),7.74(m,3H,Ph-H),7.87(m,2H,Ph-H),8.16(q,J＝6.8Hz,2H,Ph-H),8.59(m,1H,NH),8.89(m,1H,＝CH).HRMS(ESI)m/z:Calculated,384.1455,Found,384.1478[M+H]+(E)-6-methyl-3-(2-(3-nitrophenyl)hydrazine)-2-phenylquinoxaline, red-yellow solid, yield 71.9%, mp 172-175°C;1 H NMR (400MHz, CDCl3 /TMS), δ 2.55 (S, 3H, CH3 ), 7.23 (d, J=6.8Hz, 1H, Ph-H), 7.37 (d, J=6.8Hz, 1H, Ph- H), 7.63 (m, 3H, Ph-H), 7.74 (m, 3H, Ph-H), 7.87 (m, 2H, Ph-H), 8.16 (q, J=6.8Hz, 2H, Ph-H ),8.59(m,1H,NH),8.89(m,1H,=CH).HRMS(ESI)m/z: Calculated,384.1455,Found,384.1478[M+H]+
实施例4Example 4
(E)-3-(2-(3,4-二甲氧基苯基)肼)-6-甲基-2-苯基喹喔啉，红黄色固体，产率81.8％，m.p.105-108℃；1H NMR(400MHz,CDCl3/TMS),δ2.53(S,3H,CH3),4.02(S,3H,OCH3),4.05(S,3H,OCH3),7.13(t,J＝5.0Hz,1H,Ph-H),7.23(d,J＝2.0Hz,1H,Ph-H),7.34(m,1H,Ph-H),7.51-7.56(m,5H,Ph-H),7.63(m,1H,Ph-H),8.02(s,1H,Ph-H),8.09(d,J＝6.4Hz,1H,Ph-H),8.87(m,2H,1NH,1＝CH).HRMS(ESI)m/z:Calculated,399.1816,Found,399.1842[M+H]+(E)-3-(2-(3,4-Dimethoxyphenyl)hydrazine)-6-methyl-2-phenylquinoxaline, red-yellow solid, 81.8% yield, mp 105-108°C ;1 H NMR (400MHz, CDCl3 /TMS), δ 2.53 (S, 3H, CH3 ), 4.02 (S, 3H, OCH3 ), 4.05 (S, 3H, OCH3 ), 7.13 (t, J =5.0Hz,1H,Ph-H),7.23(d,J=2.0Hz,1H,Ph-H),7.34(m,1H,Ph-H),7.51-7.56(m,5H,Ph-H) ,7.63(m,1H,Ph-H),8.02(s,1H,Ph-H),8.09(d,J=6.4Hz,1H,Ph-H),8.87(m,2H,1NH,1=CH ).HRMS(ESI)m/z: Calculated,399.1816,Found,399.1842[M+H]+
实施例5Example 5
(E)-3-(2-(2-氟苯基)肼)-6-甲基-2-苯基喹喔啉，红黄色固体，产率78.7％，m.p.139-141℃；1H NMR(400MHz,CDCl3/TMS),δ2.53(S,3H,CH3),7.20(m,1H,Ph-H),7.37(q,J＝8.6Hz,2H,Ph-H),7.43(d,J＝8.2Hz,1H,Ph-H),7.47(q,J＝7.0Hz,1H,Ph-H),7.54-7.59(m,2H,Ph-H),7.72-7.76(m,2H,Ph-H),7.79(t,J＝7.2Hz,1H,Ph-H),8.87(m,2H,1NH,1＝CH).HRMS(ESI)m/z:Calculated,357.1510,Found,357.1513[M+H]+(E)-3-(2-(2-Fluorophenyl)hydrazine)-6-methyl-2-phenylquinoxaline, red-yellow solid, yield 78.7%, mp 139-141°C;1 H NMR ( 400MHz, CDCl3 /TMS), δ 2.53 (S, 3H, CH3 ), 7.20 (m, 1H, Ph-H), 7.37 (q, J=8.6Hz, 2H, Ph-H), 7.43 (d ,J=8.2Hz,1H,Ph-H),7.47(q,J=7.0Hz,1H,Ph-H),7.54-7.59(m,2H,Ph-H),7.72-7.76(m,2H, Ph-H),7.79(t,J=7.2Hz,1H,Ph-H),8.87(m,2H,1NH,1=CH).HRMS(ESI)m/z:Calculated,357.1510,Found,357.1513[ M+H]+
实施例6Example 6
(E)-3-(2-(2,4-二氯苯基)肼)-6-甲基-2-苯基喹喔啉，红黄色固体，产率60.8％，m.p.141-143℃；1H NMR(400MHz,CDCl3/TMS),δ2.53(S,3H,CH3),7.08-7.46(m,2H,Ph-H),7.60(m,4H,Ph-H),7.70(m,2H,Ph-H),8.04-8.06(m,2H,Ph-H),8.89(m,1H,＝CH).HRMS(ESI)m/z:Calculated,407.0825,Found,407.082 9[M+H]+(E)-3-(2-(2,4-dichlorophenyl)hydrazine)-6-methyl-2-phenylquinoxaline, red-yellow solid, yield 60.8%, mp141-143°C;1 H NMR (400MHz, CDCl3 /TMS), δ 2.53 (S, 3H, CH3 ), 7.08-7.46 (m, 2H, Ph-H), 7.60 (m, 4H, Ph-H), 7.70 (m ,2H,Ph-H),8.04-8.06(m,2H,Ph-H),8.89(m,1H,＝CH).HRMS(ESI)m/z:Calculated,407.0825,Found,407.082 9[M+ H]+
实施例7Example 7
(E)-6-甲基-2-苯基-3-(2-(2,3,4-三甲氧基)肼)喹喔啉，红黄色固体，产率74.5％，m.p.82-85℃；1H NMR(400MHz,CDCl3/TMS),δ2.54(S,3H,CH3),3.96(s,9H,OCH3),7.06(s,2H,Ph-H),7.56-8.60(m,8H,7Ph-H,1＝CH).HRMS(ESI)m/z:Calculated,429.1921,Found,429.1926[M+H]+(E)-6-methyl-2-phenyl-3-(2-(2,3,4-trimethoxy)hydrazine)quinoxaline, red-yellow solid, yield 74.5%, mp82-85℃;1 H NMR (400MHz, CDCl3 /TMS), δ 2.54 (S, 3H, CH3 ), 3.96 (s, 9H, OCH3 ), 7.06 (s, 2H, Ph-H), 7.56-8.60 (m ,8H,7Ph-H,1＝CH).HRMS(ESI)m/z:Calculated,429.1921,Found,429.1926[M+H]+
实施例8Example 8
(E)-6-甲基-3-(2-(2-硝基苯基)肼)-2-苯基喹喔啉，红黄色固体，产率46.0％，m.p.119-121℃；1H NMR(400MHz,CDCl3/TMS),δ2.54(S,3H,CH3),7.46-7.54(m,5H,Ph-H),7.68(t,J＝7.5Hz,1H,Ph-H),7.71-7.89(m,3H,Ph-H),8.00(d,J＝8.6Hz,2H,Ph-H),8.27(m,1H,Ph-H),8.73(m,1H,1＝CH).HRMS(ESI)m/z:Calculated,384.1455,Found,384.1456[M+H]+(E)-6-methyl-3-(2-(2-nitrophenyl)hydrazine)-2-phenylquinoxaline, red-yellow solid, yield 46.0%, mp 119-121°C;1 H NMR (400MHz, CDCl3 /TMS), δ2.54 (S, 3H, CH3 ), 7.46-7.54 (m, 5H, Ph-H), 7.68 (t, J=7.5Hz, 1H, Ph-H), 7.71-7.89(m,3H,Ph-H),8.00(d,J=8.6Hz,2H,Ph-H),8.27(m,1H,Ph-H),8.73(m,1H,1=CH) .HRMS(ESI) m/z: Calculated, 384.1455, Found, 384.1456[M+H]+
实施例9Example 9
(E)-3-(2-(4-溴苯基)肼)-6-甲基-2-苯基喹喔啉，红黄色固体，产率95.8％，m.p.139-142℃；1H NMR(400MHz,CDCl3/TMS),δ2.50(S,3H,CH3),7.45(d,J＝8.6Hz,2H,Ph-H),7.55(m,5H,Ph-H),7.63-7.66(m,3H,Ph-H),7.81(m,1H,Ph-H),8.01(s,1H,Ph-H),8.10(d,J＝8.2Hz,1H,Ph-H),8.86(m,1H,＝CH).HRMS(ESI)m/z:Calculated,417.0709,Found,417.0697[M+H]+(E)-3-(2-(4-Bromophenyl)hydrazine)-6-methyl-2-phenylquinoxaline, red-yellow solid, yield 95.8%, mp 139-142°C;1 H NMR ( 400MHz, CDCl3 /TMS), δ 2.50 (S, 3H, CH3 ), 7.45 (d, J=8.6Hz, 2H, Ph-H), 7.55 (m, 5H, Ph-H), 7.63-7.66 (m,3H,Ph-H),7.81(m,1H,Ph-H),8.01(s,1H,Ph-H),8.10(d,J=8.2Hz,1H,Ph-H),8.86( m,1H,＝CH).HRMS(ESI)m/z:Calculated,417.0709,Found,417.0697[M+H]+
实施例10Example 10
(E)-3-(2-(3-氯苯基)肼)-6-甲基-2-苯基喹喔啉，红黄色固体，产率50.0％，m.p.127-130℃；1H NMR(400MHz,CDCl3/TMS),δ2.52(S,3H,CH3),7.36(m,2H,Ph-H),7.43(d,J＝8.6Hz,1H,Ph-H),7.55(m,2H,Ph-H),7.60-7.65(m,4H,Ph-H),7.86(t,J＝10.0Hz,2H,Ph-H),8.03(s,1H,Ph-H),8.10(d,J＝8.2Hz,1H,Ph-H),8.86(m,1H,＝CH).HRMS(ESI)m/z:Calculated,373.1215,Found,373.1211[M+H]+(E)-3-(2-(3-chlorophenyl)hydrazine)-6-methyl-2-phenylquinoxaline, red-yellow solid, yield 50.0%, mp 127-130°C;1 H NMR ( 400MHz, CDCl3 /TMS), δ 2.52 (S, 3H, CH3 ), 7.36 (m, 2H, Ph-H), 7.43 (d, J=8.6Hz, 1H, Ph-H), 7.55 (m ,2H,Ph-H),7.60-7.65(m,4H,Ph-H),7.86(t,J＝10.0Hz,2H,Ph-H),8.03(s,1H,Ph-H),8.10( d,J=8.2Hz,1H,Ph-H),8.86(m,1H,=CH).HRMS(ESI)m/z: Calculated,373.1215,Found,373.1211[M+H]+
实施例11Example 11
(E)-3-(2-(2-甲氧基苯基)肼)-6甲基-2-苯基喹喔啉，红黄色固体，产率86.0％，m.p.105-108℃；1H NMR(400MHz,CDCl3/TMS),δ2.50(S,3H,CH3),3.68(s,3H,OCH3),7.12(m,1H,Ph-H),7.17-7.26(m,2H,Ph-H),7.34(d,J＝8.6Hz,1H,Ph-H),7.62(m,3H,Ph-H),7.89(m,2H,Ph-H),8.06(d,J＝8.2Hz,1H,Ph-H),8.88(m,2H,1NH,1＝CH).HRMS(ESI)m/z:Calculated,369.1710,Found,369.1711[M+H]+(E)-3-(2-(2-methoxyphenyl)hydrazine)-6methyl-2-phenylquinoxaline, red-yellow solid, yield 86.0%, mp 105-108°C;1 H NMR (400MHz, CDCl3 /TMS), δ2.50 (S, 3H, CH3 ), 3.68 (s, 3H, OCH3 ), 7.12 (m, 1H, Ph-H), 7.17-7.26 (m, 2H, Ph-H), 7.34 (d, J=8.6Hz, 1H, Ph-H), 7.62 (m, 3H, Ph-H), 7.89 (m, 2H, Ph-H), 8.06 (d, J=8.2 Hz,1H,Ph-H),8.88(m,2H,1NH,1＝CH).HRMS(ESI)m/z:Calculated,369.1710,Found,369.1711[M+H]+
实施例12Example 12
(E)-6-甲基-3-(2-(4-甲基苯基)肼)-2-苯基喹喔啉，红黄色固体，产率80.7％，m.p.240-243℃；1H NMR(400MHz,CDCl3/TMS),δ2.52(S,3H,CH3),2.56(s,3H,CH3),7.46(m,4H,Ph-H),7.61(m,2H,Ph-H),7.63(m,2H,Ph-H),8.00(s,1H,Ph-H),8.07(d,J＝6.8Hz,1H,Ph-H),8.88(m,3H,1Ph-H,1NH,1＝CH).HRMS(ESI)m/z:Calculated,353.1761,Found,353.1764[M+H]+(E)-6-methyl-3-(2-(4-methylphenyl)hydrazine)-2-phenylquinoxaline, red-yellow solid, yield 80.7%, mp 240-243°C;1 H NMR (400MHz, CDCl3 /TMS), δ 2.52 (S, 3H, CH3 ), 2.56 (s, 3H, CH3 ), 7.46 (m, 4H, Ph-H), 7.61 (m, 2H, Ph- H), 7.63(m, 2H, Ph-H), 8.00(s, 1H, Ph-H), 8.07(d, J=6.8Hz, 1H, Ph-H), 8.88(m, 3H, 1Ph-H) ,1NH,1＝CH).HRMS(ESI)m/z:Calculated,353.1761,Found,353.1764[M+H]+
实施例13Example 13
(E)-3-(2-(2-(呋喃-3-基)亚苄基)肼)-6-甲基-2-苯基喹喔啉，红黄色固体，产率78.9％，m.p.123-126℃；1H NMR(400MHz,CDCl3/TMS),δ2.55(S,3H,CH3),6.78(m,1H,furan-H),7.17(d,J＝3.2Hz,1H,furan-H),7.34(m,1H,Ph-H),7.48(m,1H,Ph-H),7.62(m,3H,Ph-H),7.82(m,1H,furan-H),8.02(s,1H,Ph-H),8.10(d,J＝8.2Hz,1H,Ph-H),8.85(m,3H,1Ph-H,1NH,1＝CH).HRMS(ESI)m/z:Calculated,329.1397,Found,329.1407[M+H]+(E)-3-(2-(2-(furan-3-yl)benzylidene)hydrazine)-6-methyl-2-phenylquinoxaline, red-yellow solid, 78.9% yield, mp123- 126°C;1 H NMR (400MHz, CDCl3 /TMS), δ 2.55 (S, 3H, CH3 ), 6.78 (m, 1H, furan-H), 7.17 (d, J=3.2Hz, 1H, furan -H), 7.34(m, 1H, Ph-H), 7.48(m, 1H, Ph-H), 7.62(m, 3H, Ph-H), 7.82(m, 1H, furan-H), 8.02( s, 1H, Ph-H), 8.10 (d, J=8.2Hz, 1H, Ph-H), 8.85 (m, 3H, 1Ph-H, 1NH, 1=CH). HRMS(ESI) m/z: Calculated,329.1397,Found,329.1407[M+H]+
实施例14Example 14
(E)-3-(2-(4-异丙基苯基)肼)-6-甲基-2-苯基喹喔啉，红黄色固体，产率61.8％，m.p.137-140℃；1H NMR(400MHz,CDCl3/TMS),δ1.72(t,J＝7.2Hz,6H,CH3),2.60(S,3H,CH3),3.93(m,1H,CH3),7.50(d,J＝8.4Hz,1H,Ph-H),7.59(m,4H,Ph-H),7.98(s,1H,Ph-H),8.00(s,1H,Ph-H),7.62(m,3H,Ph-H),8.10(m,1H,Ph-H),8.84(m,2H,1NH,1＝CH).HRMS(ESI)m/z:Calculated,303.1615,Found,303.1605[M-H]-(E)-3-(2-(4-isopropylphenyl)hydrazine)-6-methyl-2-phenylquinoxaline, red-yellow solid, yield 61.8%, mp 137-140°C;1 H NMR (400 MHz, CDCl3 /TMS), δ 1.72 (t, J=7.2 Hz, 6H, CH3 ), 2.60 (S, 3H, CH3 ), 3.93 (m, 1H, CH3 ), 7.50 (d , J=8.4Hz, 1H, Ph-H), 7.59(m, 4H, Ph-H), 7.98(s, 1H, Ph-H), 8.00(s, 1H, Ph-H), 7.62(m, 3H,Ph-H),8.10(m,1H,Ph-H),8.84(m,2H,1NH,1＝CH).HRMS(ESI)m/z:Calculated,303.1615,Found,303.1605[MH]-
实施例15Example 15
(E)-3-(2-亚乙基肼)-6-甲基-2-苯基喹喔啉，红黄色固体，产率60.9％，m.p.90-93℃；1H NMR(400MHz,CDCl3/TMS),δ2.54(S,3H,CH3),2.57(s,3H,CH3),7.48(m,1H,Ph-H),7.52-7.57(m,5H,Ph-H),7.62(s,1H,Ph-H),7.62(m,3H,Ph-H),7.87(d,J＝6.8Hz,1H,Ph-H).HRMS(ESI)m/z:Calculated,275.1302,Found,275.1293[M-H]-(E)-3-(2-Ethylenehydrazine)-6-methyl-2-phenylquinoxaline, red-yellow solid, yield 60.9%, mp 90-93°C;1 H NMR (400MHz, CDCl3 /TMS), δ2.54(S, 3H, CH3 ), 2.57(s, 3H, CH3 ), 7.48(m, 1H, Ph-H), 7.52-7.57(m, 5H, Ph-H), 7.62(s,1H,Ph-H),7.62(m,3H,Ph-H),7.87(d,J＝6.8Hz,1H,Ph-H).HRMS(ESI)m/z:Calculated,275.1302, Found,275.1293[MH]-
实施例16抗真菌性测试Example 16 Antifungal Test
试验对象：尖孢炭疽菌，草莓炭疽菌，枸杞炭疽病菌。Test objects: Anthracnus oxysporum, Anthracnus anthracis of strawberry, Anthracnus anthracis of Lycium barbarum.
接种方法：用一个L形玻璃棒将各真菌物种的分生孢子轻轻刷到薄层板。Inoculation method: Use an L-shaped glass rod to gently brush conidia of each fungal species onto a thin-layer plate.
直接生物自显影：等测试结束后，测量薄层色谱版的半径大小。Direct bioautography: After the test is over, measure the radius of the TLC plate.
抗菌活性测试结果如表1所示The antibacterial activity test results are shown in Table 1.
表1化合物B1-B16的杀菌活性数据Table 1 Bactericidal activity data of compounds B1-B16
从表1抗菌活性表明，化合物B15在微量滴定条件下对真菌尖孢炭疽病菌、草莓炭疽病菌和枸杞炭疽病菌均有良好的活性，化合物B1、B2、B6、B10、B13、B14对三种靶标有一定杀菌活性。The antibacterial activity in Table 1 shows that compound B15 has good activity against fungi anthracnose, strawberry anthracnose and wolfberry anthracnose under microtitration conditions. Has a certain bactericidal activity.
具体化合物结构如表2所示The specific compound structures are shown in Table 2.
表2化合物B1-B15的具体结构Table 2 Specific structures of compounds B1-B15
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| CN201610617529.7ACN106234373B (en) | 2016-07-28 | 2016-07-28 | A kind of application of hydrazone compounds of the structure of benzopyrazines containing methyl as fungicide |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2013034755A1 (en)* | 2011-09-09 | 2013-03-14 | H. Lundbeck A/S | Triazolopyrazine derivatives and their use for treating neurological and psychiatric disorders |
| CN103224470A (en)* | 2013-05-17 | 2013-07-31 | 南京农业大学 | Preparation method and application of quinoxaline-6-phenylhydrazone derivants |
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2013034755A1 (en)* | 2011-09-09 | 2013-03-14 | H. Lundbeck A/S | Triazolopyrazine derivatives and their use for treating neurological and psychiatric disorders |
| CN103224470A (en)* | 2013-05-17 | 2013-07-31 | 南京农业大学 | Preparation method and application of quinoxaline-6-phenylhydrazone derivants |
| Title |
|---|
| Quinoxaline derivatives part II: Synthesis and antimicrobial testing of 1,2,4-triazolo[4,3-a]quinoxalines, 1,2,4-triazino[4,3-a]quinoxalines and 2-pyrazolylquinoxalines;S.A.El-HAWASH, et al;《Pharmazie》;19991231;第54卷;第808页"Scheme 1"部分，第810页Table 1、Table2部分* |
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