Synthesis And Application Of Novel Trifluoromethyl Indoles Based On Coumarins

In the research of new agrochemicals,using natural or biological active substances to create new green agrochemicals,by introducing functional heterocyclic rings or heteroatoms in the structure of natural active substances is an effective method to develop new higher active agrochemicals in recent years.In this paper,a series of fluoro-containing coumarins attached to indoles were synthesized by one-pot method in the present of protonic acid as a catalyst.These compounds which includes bis(indolyl)core,furan ring or thiophene ring were all synthesized from an intermediate of tertiary trifluoroethanol which was obtained by treatment of ?-trifluoroacetyl-coumarin with indole using Lewis acid as catalyst.The details of the research are shown as follows:1.Research on the reaction of ?-trifluoroacetylcoumarin with indole and the antibacterial activity of the productsIn the present of Sc(OTf)₃ and p-TSA as catalysts,using ?-trifluoroacetylcoumarin and double equivalent indole as reactants,a series of novel fluoro-containing coumarins derivatives with bis(indolyl)core were synthesized by one-pot method,which contained 23 compounds and showed the wide applicability of the reaction.The products were characterized by 1H-NMR,13C-NMR,19F-NMR,HRMS and IR to determine the structure.Besides,two single crystals were obtained by the solvent evaporation and their X-ray diffraction data were both consistent with the expected structure,which confirmed the structure of target products.Finally,the bioactivity of the synthesized target compounds were tested.For Fusarium pseudograminearum,when the drug concentration was 500 ?g/mL,the antibacterial effect of the target products(4f,4g,4i,4o,4q,4s)was the best.The antibacterial rate was 65?74%,which could inhibit the growth of fungus effectively,indicating that the antibacterial effect was better when the compounds contained electron-withdrawing groups.F or Fusarium moniliforme,the antibacterial effect of the synthetic compounds was ordinary and the antibacterial rate of most compounds was only 42?49%;For Curvularia lunata,when the drug concentration was 500 ?g/mL,The results showed that the inhibition rate of the target product was significantly high and the inhibition effect was particularly obvious.The inhibition rate was 70?81%,which indicated that it was more effective to C.urvularia lunata.For Phytophtora nicotianae,the inhibition effect of the target product was not particularly ideal,and the inhibition rate was between 41-50%.By comparison,the inhibition effect was better when there were electron-withdrawing groups on the coumarin ring.2.Research on the reaction of fluorinated monoindole tertiary alcohols with furansBased on the tertiary trifluoroethanols containing a coumarin ring and a indole ring,which were generated by ?-trifluoroacetylcoumarin and equivalent indole under the catalysis of Sc(OTf)₃,a series of novel fluorinated coumarin derivatives which contains three heterocyclics(coumarin,indole and furan)attached to a carbon atom were synthesized by one-pot method in the present of TFA as a catalyst.30 target products were obtained and characterized by 1H-NMR,13C-NMR,19F-NMR,HRMS and IR.Three of them were obtained as a single crystal by solvent evaporation.X-ray diffraction data was consistent with the expected structure,which confirmed the structure of target products.Besides,the spatial distribution among the three heterocyclics can be clearly observed from the packing views of the single crystal structures.3.Research on the reaction of fluorinated monoindole tertiary alcohols with thiophenesBased on the tertiary trifluoroethanols containing a coumarin ring and a indole ring,which were generated by P-trifluoroacetylcoumarin and equivalent indole under the catalysis of Sc(OTf)₃,a series of novel fluorinated coumarin derivatives which contains three heterocyclics(coumarin,indole and thiophene)attached to a carbon atom were synthesized by one-pot method in the present of TFA as a catalyst.5 target products were obtained and characterized by 1H-NMR,13C-NMR,19F-NMR,HRMS and IR.4.Study on the reaction of ?-trifluoroacetylcoumarin with 3-substituted indoleBased on the previous Friedel-Crafts reaction of C3 of indole,the reaction of ?-trifluoroacetylcoumarin with 3-substituted indole was carried out in the present of Sc(OTf)₃ as a catalyst and the addition of C2 of indole with carbonyl was achieved to form a tertiary trifluoroethanol attached to C2 of indole.The target products were characterized by 1H-NMR,13C-NMR,19F-NMR,HRMS and IR.The structure was also confirmed by single crystal X-ray diffraction.