The Synthesis Of Six Isocoumarin Derivatives

Plant is the treasure of natural active compounds. It is becoming an important way to extract some substances with bioactive activity from plants and to transform the structure of the substances in the development of new type of pesticides. At present, the study of botanical insecticides and fungicide have been widely reported, while the study of herbicide is not much.In previous study, some substances with strong herbicidal activity which proved to isocoumarin compound were extracted from Flaveria bident(L.) Kuntze. The structure of substance was transformed using chemistry synthesis method, and 3-hexyl-4- cyan-6,7-dimethoxy isocoumarin were got. In present study, it was based on the former research to synthesis another substances, two aspects were summarized as bellow:1.Synthesis of 3-hexyl-6,7- dimethoxy isocoumarin-4- carboxylic acid from 3-hexyl-4- cyan-6,7- dimethoxy isocoumarin.Firstly,we use the method of historical documents. W ith copper oxide as catalyst,the cyano of Cyano synthesis reacted with Acetaldehyde oxime.As a result,the cyano became into Formamide through hydrolysis. Solvent by copper oxid e,we finally selected reaction conditions for 0.1 equivalent copper oxide as well as acetald ehyde oxime 1.5 equivalent, with DMF reflowing for 12 h and the conversion rate is 52.41%. Because Cuprous halide can catalyze a variety of organic reactions,it’s commonly used in the chemical synthesis of copper catalyst.When we replaced Copper oxide with Cuprous halide,both the conversion rate and time in this reaction had been improved.The conversion rate increased significantly and the time shortened. Ultimately,the condition selected for this reaction is using 0.1 equivalent cuprous iodide as well as acetaldehyde oxime 1.5 equivalent, with DMF reflowing for 0.5h and then the conversion came to 85.69%.2.The first method was indirect synthesis technique. Firstly, under the catalyst copper halide and cuprous oxide, 3-hexyl-4- cyan-6,7- dimethoxy isocoumarin reacted with acetaldoxime and 3-hexyl-6,7-dimethoxy isocoumarin-4- carboxamide were got. Then 3-hexyl-6,7-dimethoxy isocoumarin-4- carboxylic acid were got with the reaction of 3-hexyl-6,7-dimethoxy isocoumarin-4- carboxamide and Na NO2. The advantages of first step is the high conversion rate and good directionality, from which pure 3-hexyl-6,7-dimethoxy isocoumarin-4- carboxamide can be got. However, the conversion rate in step 2 was a little lower. Another method was direct hydrolysis. In this method, 3-hexyl-4-cyan-6,7-dimethoxy isocoumarin was dissolved into 80% of the sulfuric acid in acetic acid, then reacting with the condition 80 ℃ for 6h, the 3-hexyl-6,7-dimethoxy isocoumarin-4- carboxamide will be got directly. This the advantages of this method is the few steps and the easy reaction condition without the use of catalyzes. So it was an ideal way to get 3-hexyl-6,7-dimethoxy isocoumarin-4- carboxylic acid.3.Following the Suzuki reaction theory, with the using of 3-hexyl-4- iodo-6,7-dimethoxy isocoumarin(a former substance of 3-hexyl-4- cyan-6,7-dimethoxy isocoumarin) as a raw material reacted with boric acid compounds under the catalyzing of Pd(0),there are four isocoumarin derivatives generated named as 3-hexyl-4-(4-fluorophenyl)-6,7-dimethoxy isocoumarin, 3-hexyl-4-(3-fluorophenyl)-6,7-dimethoxy isocoumarin, 3-hexyl-4-(4-(trifluoromethyl)phenyl)-6,7-dimethoxy isocoumarin, 3-hexyl-4-(3-(trifluoromethyl)phenyl)- 6,7- dimethoxy isocoumarin, respectively. This four compounds were new types of isocoumarin derivatives which used fluorobenzene instead of the Alaninamide in the precursor 4-(2- amino acrylic amide)-3-5,6,8,4,5,6,7,8,9,10- eight hydrogen- 3 hydroxy- 3- methyl isopropyl coumarin.4.After a small cup text of the four synthetic compounds about herbicidal activity, thre e derivatives of them exhibited good inhibition of weeds and showed good role in promotin g sorghum. Wherein the 3-hexyl-4-(4-fluorophenyl)-6,7-dimethoxy isocoumarin and 3-he xyl-4-(3-fluorophenyl)-6,7-dimethoxy-fragrant coumarin showed Amaranthus root inhibit ion and another compound 3-hexyl-4-(4-trifluoromethylphenyl)-6,7-dimethoxy isocoumar in exhibited of foxtail inhibition of dog tail grass root. With the connection of law structura l formula among three compounds and the rules in IC50, I conducted a structure-activity re lationship analysis, the conclusion showed that the phenyl-substituted derivatives of herbic idal activity was higher in para arrangements compared with meta-derivatives and the bioa ctivity in derivatives of fluorobenzene was higher than the trifluoromethyl derivatives. The structure-activity relationship within those three active compounds needs further research, which will lay the foundation for further study of the structure and mechanism of transform ation.In present study, based on the known coumarin material with herbicidal activity, some reactions were done in order to get lead compounds with higher herbicidal activity and to find new effect targets of herbicides. The synthesis provides a theoretical basis for the development of new herbicides.