Synthesis And Herbicidal Activity Of Tetramic Acid Derivatives Containing Ether Moiety

Tenuazonic acid（TeA）,a secondary metabolite of Alternaria alternata,has many biological activities,such as antitumor,antiviral and bactericidal.The herbicidal activity of TeA was especially prominent,which has attracted extensive attention of scholars.A large number of tetramic acid derivatives have been synthesized by introducing various substituents at different positions of the pyrrole ring and some of them showed different degrees of herbicidal activity.Ether group is a common active group in the molecular structure of herbicides,fungicides and insecticides.In recent years,some new developed herbicides,containing ether groups in their structures,not only have more satisfying herbicidal activity,toxicity and environmental compatibility,but also have excellent safety and conductivity.In order to screen new compounds with herbicidal activity,twenty-five novel tetramic acid derivatives containing ether groups were designed and synthesized by introducing substituted ether groups at the nitrogen atom of 3-acylpyrrolidine-2,4-dione.And their herbicidal activities were preliminarily evaluated.Firstly,eighteen substituted phenols were reacted successively with N-（2hydroxyethyl）phthalimide and hydrazine hydrate to prepare 2-（substituted aryloxy）ethylamines.Then,2-alkoxyalkylamines and 2-（substituted aryloxy）ethylamines were used as the starting materials to synthesize four tetramic acid derivatives containing alkoxyalkyl moiety 8a-8d and twenty-one tetramic acid derivatives containing substituted aryloxyethyl moiety 12a-12u by the reactions of substitution,acylation,cyclization and acidification.The synthesized target compounds were confirmed by FT-IR,1H NMR,13C NMR and HR-MS analysis.The compound 12a was dissolved in methanol,and the colorless lamellar single crystal was cultured and obtained by solvent volatilization method.The single crystal structure was analyzed by X-ray diffraction.The SHELXL-2014/7 program was used to analyze the structure and refine the results.The crystal belongs to Triclinic,the space group is P 1.The edge lengths of the unit cell are:a=8.0404（7）?,b=13.5575（9）?,c=14.0775（7）A.The angles between the edges of the unit cell are:α=68.6495（5）°,β=76.420（6）°,γ=81.852（6）°.The crystal density is 1.417 g/cm3 and the volume is 1386.26（18）?³.The total deviation factor R=0.0473,wR²=0.1422,S=1.04.In the Fourier diagram,the highest residual electron density peak（Δρ）_max=0.23 e?^-3,and the lowest residual electron density peak（Δρ）_max=-0.30 e?^-3.Through the crystal structure analysis of compound 12a,the 3-position acyl group of the target compounds exists in the form of 1-hydroxyethylidene,and the C=C double bond linking the pyrrolidine-2,4-dione ring shows a Z-configuration.The herbicidal activity of target compounds against Echinochloa crusgalli（L.）Beauv.and Brassica campestris L.was determined by the dish method.At the concentration of 100μg/mL,the target compounds showed different degrees of herbicidal activities against the tested Echinochloa crusgalli（L.）Beauv.and Brassica campestris L.The inhibition rates of five compounds against the stem length of Echinochloa crusgalli（L.）Beauv.were more than 40%,of which the inhibition rate of compound 12t was 51.8%,which was close to 53.0%of the control drug TeA.Nine compounds inhibited more than 40%of Echinochloa crusgalli（L.）Beauv.root length,among which the inhibition rates of comounds 8a,12j and 12q were 53.6%,55.5%and 65.6%,respectively.The inhibition rates of ten compounds against the root length of Brassica campestris L.were over 40%,among which the inhibition rates of compounds 8d,12c,12j,12n and 12o were 52.0%,51.0%,53.0%,84.0%and 56.5%,respectively.Most of the target compounds showed the negative correlation between the herbicidal activities of Echinochloa crusgalli（L.）Beauv.and Brassica campestris L.,indicating that they have certain selectivity between monocotyledons and dicotyledons.By analyzing the herbicidal activity data against Echinochloa crusgalli（L.）Beauv.of the target compounds,it can be found that in the series of compounds 8a-8d,the compound 8a containing the methoxyethyl moiety had the highest inhibition rate against the growth of stems and roots of Echinochloa crusgalli（L.）Beauv.,while the activities of other three compounds containing the alkoxypropyl moiety were relatively low,but the herbicidal activities of these three compounds increased gradually with the extension of alkyl carbon chain.Among the series of compounds 12a-12u,the herbicidal activities of compounds with the substituent H,2-Cl,2,4-Cl₂ and 2-OCH₃ at the benzene ring were relatively high,indicating that the substitutions at 2-position of benzene ring were beneficial to improve the herbicidal activity against Echinochloa crusgalli（L.）Beauv..By analyzing the herbicidal activity data against Brassica campestris L.,of the target compounds,it can be found that among the series of compounds 8a-8d,the compound 8d with the longest alkyl group had the highest activity.Among the series of compounds 12a-12u,the herbicidal activities of compounds with the substituent H,4-Cl,2,4,6-Cl₃,4-CH₃ and 4-OCH₃ at the benzene ring were relatively high,which indicates that the substitutions at 4-position of benzene ring were beneficial to improve the herbicidal activity of Brassica campestris L..