DFT Investigations Of The Mechanisms For C-H Activation And Huisgen Cycloaddition Reaction

This thesis is subject to investigate the mechanisms of aryl-H cyanation,Csp3-H activation of ethyl 2-(p-tolylamino)acetate and Huisgen cycloaddition reaction between N-methylindole and sulfonylazides with DFT method.In the first part,the mechanism of selective C-H cyanation of 2-phenylpyridine catalyzed by CuBr was investigated with DFT method at the B3LYP/6-31+G(d,p)level,and the integral equation formalism polarized continuum model(IEFPCM)was applied to simulate the solvent effect.The computational results suggested that 2-phenylacetonitrile can convert into benzoyl cyanide under O2 condition via two paths(a and b),and also,2-phenylacetonitrile can first react with O2-anion to get 2-hydroxy-2-phenylacetonitrile,and then 2-hydroxy-2-phenylacetonitrile goes through an oxidative dehydrogenation to yield benzoyl cyanide via four different paths(c,d,e and f).The other part reaction of the conversion of 2-phenylpyridine to the2-(pyridin-2-yl)-benzonitrile catalyzed by CuBr can go through three paths(g,h and i)which involve the coordination of CN-and N atom of 2-phenylpyridine with Cu cations,and then the processes of addition and oxydehydrogenation reactions lead to the final product2-(pyridin-2-yl)benzonitrile.In addition,another path(j)without participation of CuBr could also occur.The results could provide valuable insights into these types of interactions and related ones.In the second part,the mechanisms of the reactions between ethyl 2-(p-tolylamino)acetate and oxygen,substituted with hydrogen atom and methyl,and initiated by TBPA to produce indole derivatives and quinoline derivatives,were investigated using DFT method.Also the SMD model was applied to simulate the solvent effects.Fukui functions and dual descriptor have been employed to assess the atomic reactivity.In this part,the Csp3-H activation of these two reactions have four possible paths.The computational results show that the first reaction would continue to react with oxygen to produce 1,5-dimethylindoline-2,3-dione via two possible paths after Csp3-H activation.And the better path is to lose the CH3 CHO and H2 O continuously.The second reaction would continue to have one dehydrogenation reaction to generate the double bond after Csp3-H activation.Then it reacts with phenylethylene to produce six-membered ring compound.At last,a series of oxidative dehydrogenation reactions happened to yield the6-methyl-4-phenylquinoline-2-carboxylate.The computational results not only agree with experimental phenomena,but also can provide theoretical support for the optimization reaction.In the third part,the mechanisms of three cascade reactions between N-methylindole and sulfonylazides via Huisgen cycloaddition were investigated using density functional theory(DFT),and the polarized continuum model(PCM)was applied to simulate the solvent effects.Fukui functions and dual descriptor have been employed to assess the atomic reactivity.With respect to these three reactions,each has two possible reaction pathways(I and II).The calculated results show that singlet O2 plays a crucial role in the oxidative dehydrogenation process in the first reaction between 2-imine indole and p-tosylazide(TsN3),when the reaction occurs without O2 but with N2,two pathways via the processes of breaking two covalent bonds,followed by 1,2-H shift and N2 removal(or by N2 removal and 1,2-H shift)exist.Water molecule plays an important role in the H-shift process in the third reaction of the methyl substituted N-methylindole with TsN3.Our results demonstrated that these reactions can take place at certain condition,in good agreement with the experimental observation.The understanding of the competitive pathways for Huisgen cycloaddition of N-methylindole and sulfonylazides can provide valuable insights into related reactions.