| The utilization of safer solvents, designing for energy efficiency, and utilizing catalysts among 12 principles of green chemistry are the three key principles of relevance to synthetic chemistry. The emerging areas for achieving this target are to explore alternative reaction media and reaction conditions to design new chemical processes. To obtain activation parameters, quantum chemistry can precision predict the most favorable pathway and the corresponding structures of transition states under different reaction conditions via solving Schr?dinger equations. Especially for the mechanism explanation, computational chemistry has become one of the essential tools. In this work, we focused on computational investigation on the effect of reaction conditions on the mechanism, which is easily neglected in experiment. To achieve green syntheses, we explore the effect of assistant(catalyst), solvent, and counterion on the reactions to optimize the experimental conditions. The results are shown as following:The mechanism of the intramolecular anti-Michael addition of N-alkylfurylacrylacetamides is investigated by B3LYP/6-31G(d,p) functional calculations. Three possible reaction pathways have been considered based on possible conformations of the same reactant, which undergoes three stages, including hydrogen elimination by the base Na H, followed by the nucleophilic addition of N- on Cα(Cβ) via an anti-Michael(Michael) mechanism, and then proton transfer affords the ?nal product Pr-5(Pr-6). The pathway corresponding to the reactant with the most stable conformation is found to be the most favorable one. The rate-determining step of the intramolecular nucleophilic addition is the nucleophilic addition of N- on Cα(Cβ) featuring a cyclic ring transition state. Solvent effects are considered at the B3LYP/6-31G(d,p) level in solvent DMSO, and the results suggest that the relative reaction trends are consistent with the gas-phase reaction. Furthermore, the difference of the energy barriers explains the origin of the regioselectivity of the experiment. Finally, the effects of the substituent on N1 and Cβ to the regioselectivity were further discussed. This result expands the range of the effective substrates for anti-Michael reactions.A density functional theory(DFT) study was performed to elucidate the mechanism for the [5+1] benzannulation of nitroethane and α-alkenoyl ketene-(S,S)-acetals. The calculation results are consistent with experimental findings, showing that the reaction proceeds via deprotonation of nitroethane, nucleophilic addition, intramolecular cyclization, elimination of HNO2, and the keto-enol tautomerization sequence. It was disclosed that DMF and DBU act as not only solvent and non-nucleophilic base, respectively, but also catalysts in the reaction by stabilizing the transition states and intermediates via intermolecular hydrogen bonds and electrostatic interactions. Besides, the effective orbital interaction of the reaction site in transition state also contributes to the intramolecular cyclization step. The new mechanistic insights obtained by DFT calculations highlight that the hydrogen bonds and electrostatic interactions are key factors for the [5+1] benzannulation of nitroethane and α-alkenoyl ketene-(S,S)-acetals. This study contributes significantly to our understanding of the combination model between substrates and solvent as well as base for the synthesis of [5+1] annulations, which provides a theoretical basis for further designing reactions.DFT investigations are carried out to improve the domino cyclization between gem-dialkylthio vinylallenes and benzylamine to achieve green synthesis. Green reaction approaches were explored, namely, this reaction can occur under organic solvent-free conditions either catalyzed by trace water or self-catalyzed by Bn NH2. Three types of reactions(DMSO-assisted, trace water-catalyzed and self-catalyzed by Bn NH2) shared the same reaction mechanism M1 with the nucleophilic attack of Bn NH2 to the allenic carbon of thioamide intermediate Re. For trace water-catalyzed reaction another mechanism M2 was also found that is the Bn NH2 attacks the carbonyl carbon of the conformational isomer of Re. Among the investigated mechanisms, the trace water-catalyzed one is suggested to be the most efficient and convenient synthetic method for pyrroles. Our calculated results imply that organic solvent DMSO is not necessary in this reaction. These were further confirmed by the experimental observation, which opens a new strategy for the synthesis of pyrroles and implements the guiding role of theoretical research in experimental synthesis.DFT investigations are carried out to explore the effective catalyst forms of DBU and H2 O and the mechanism for the formation of 2,3-dihydropyrido[2,3-d]-pyrimidin-4(1H)-ones. Three main pathways are disclosed under unassisted, water-catalyzed, DBU and water co-catalyzed conditions, which involves concerted nucleophilic addition and H-transfer, concerted intramolecular cyclization and H-transfer, and Dimroth rearrangement to form the product. The results indicated that the DBU and water co-catalyzed pathway is the most favoured one as compared to the rest two pathways. The water donates one H to DBU and accepts H from 2-amino-nicotinonitrile(1), forming [DBU-H]+-H2 O as effective catalyst form in the proton migration transition state rather than [DBU-H]+?OH-. The hydrogen bond between [DBU-H]+···H2O···1- decreases the activation barrier of the rate-determining step. Our calculated results open a new insight for the green catalyst model of DBU-H2 O.Two reaction mechanisms of NBS and chalcones are investigated using B3LYP/6-31+G(d,p) method. DBU-catalyzed NBS reacts directly with chalcones as well as the reaction of NBS and water molecules then with chalcones by stepwise process, respectively. The calculation results indicated that the stepwise mechanism is the most favored one. It undergoes three processes, containing the formation of succinimide and hypobromous acid, water-catalyzed the nucleophilic addition with simultaneous depronation and protonation, and water-catalyzed the keto-enol tautomerization. We found that water molecules play vital roles in the whole reaction: stabilizer and proton shuttle. In addition, the combination sites between water and substrate will affect the activation barriers of the keto-enol tautomerization step, and the three-water assisted process is the most favored one in comparison with others. The electrostatic interactions between DBU and NBS as well as C-H···O, O-H···O, and C-H···π hydrogen interactions effectively stabilize the structures of transition states and promotes the reaction. These results provide a universal mechanism for DBU-catalyzed reaction of NBS with chalcones and guidance for experimental researchers. |
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