Study On Palladium Catalysed Synthesis Of Benzoheterocyclic Compounds And Their Biological Activity

Transitional palladium(Pd)has attracted much attention from organic chemists because of its high catalytic activity and excellent selectivity.It has been widely used as a catalyst in various coupling reactions.The benzo-five-membered heterocycles widely existed in the nature and also showed important bioactivities.Therefore,the synthesis of these compounds are popular in the field of organic synthesis.At present,in synthetic methods of synthesis of the benzo-five-membered heterocycles,Palladium catalyzed tandem reaction is the main one,including cyclization/couping,couping/cyclization,Wacker type reaction,Catellani type reaction,ect.These methods have made great progress,but there are still some shortcomings and need to be improved.The formation of carbon-carbon bond by metal-catalyzed activation of carbon-hydrogen bond is not only an attractive strategy,which doesn’t need specific functional groups to participate in the reaction,but also reduces by-products,which meets with the principles of atomic economy in green chemistry.Based on the previous studies,We used the(1)-BINAP phosphine as a ligand to further explore the palladium-catalyzed cy clization/C-H activation to construct the benzo-heterocyclic compounds,and some copmpounds were studied on the bioacitivity.The exploration of this thesis mainly includes the following aspects:1.We screened a series of the conditions,including palladium catalysts,ligands,bases,solvents,temperature and additives ect,by using 1-bromo-2-((2-methylallyl)oxy)benzene and benzo[b]thiophene as model substrates.The optimum reaction conditions was:5mmol%Pd(PPh3)2Cl2,6mmol%(±)-BINAP,2.0eq K2CO3,0.3eq PivOH,DMA/110℃/30 h.2.With the optimal conditions,the substrates were expanded including different kinds of bromoarenes,and also inchuding benzo[b]thiophene,benzofuran,indole,benzo[d]thiazole,benzo[d]oxazole,thiophene ect aromatic ring.Finally,we successfully synthesized 51 benzofurans,indoles,indolones and isobenzopyrans derivatives,which the highest yield was up to 92%.3.The part of the obtained compound was subjected to a bioactivity test.The effect of the sample on the Penicillium was determined by the filter paper method.The preliminary results showed that the compound 4b had certain inhibitory effect on Penicillium at lmg/mL.The effect of Mycobacterium smegmatis was measured by Alma blue.The preliminary results showed that the tested samples had no inhibitory effect on Mycobacterium smegmatis at 40μg/mL.