Search

The mechanisms of the synthesis of 2‐substituted‐3‐(1H‐indol‐3‐yl)‐isoindolin‐1‐one derivatives have been investigated theoretically under unassisted, self‐assisted, and water‐assisted conditions. Being different from previously proposed catalyst‐free by Hu et al., our results show that the title mechanism can be altered and accelerated by solvent and substrate 2. Two types of mechanisms have been developed by DFT calculations differ in the reaction sequence of substrates 1 with 3 (M1) or 2 (M2) followed by 2 (M1) or 3 (M2), and water‐assisted M1 is the most favored one. It was found that the nucleophilicity of substrate 3 is stronger than that of 2. Our calculations suggest that the water‐assisted pathway in M1 is the most favorable case, which undergoes nucleophilic addition and H‐shift, C–N bond formation and water elimination, and intramolecular cyclization and water elimination. The rate‐determining step is the nucleophilic attack process. Moreover, we also explored the effect of nucleophilic attack of the nitrogen of (4‐methoxyphenyl)methanamine on hydroxyl or carbonyl group carbon of phthalaldehydic acid on the activation energy. More importantly, we found that water molecules play a critical role in the whole reaction, not only act as solvent but also as an efficient catalyst, proton shuttle, and stabilizer to stabilize the structures of transition states and intermediates via π···H−O, O···H−N, O···H−C, and O···H−O interactions. The origin of the different reactivity of M1 and M2 is ascribed to the pivotal noncovalent interactions exist between catalyst (water and substrate 2) and reactants. © 2018 Wiley Periodicals, Inc. The new water‐catalyzed mechanism M1 provides an efficient and convenient green synthetic strategy for 2‐substituted‐3‐(1H‐indol‐3‐yl)‐isoindolin‐1‐one and their derivatives. [ABSTRACT FROM AUTHOR]

The mechanism of N‐Bromosuccinimide (NBS) promoted synthesis of imidazo[1,2‐a]pyridine in water as well as the effective activation modes of NBS was investigated by Density Functional Theory (DFT) calculations. Two main mechanisms that differ in the reaction sequence of substrate were explored: styrene with NBS then followed by 2‐aminopyridine (M1) or simultaneously with NBS and 2‐aminopyridine (M2), and water‐assisted M2 is the more favored one. We found that the adding sequence of 2‐aminopyridine affects profoundly on the title reaction. Moreover, upon the assistance of water and NBS, the preferential mechanistic scenario involves three major processes: nucleophilic addition, stepwise H‐shift and intramolecular cyclization, three‐step deprotonation, rather than a classical bromonium ion species. Specifically, the cooperative interaction of NBS and water plays a critical role in the title reaction. Water acts as solvent, reactant, anchoring, stabilizer, and catalyst. NBS promotes the above three processes by the effective forms of Br+/Br−, succinimide, and its ethanol isomer. Furthermore, noncovalent interactions between catalysts and substrates are responsible for the different reactive activities of M1 and M2. Our results indicate that simultaneous adding of all reactants is recommended toward economical synthesis. © 2018 Wiley Periodicals, Inc. DFT calculations disclosed a H2O‐NBS cooperated preferential synthesis strategy of imidazo[1,2‐a]pyridine differ in the reaction sequence of substrates. [ABSTRACT FROM AUTHOR]

Silver-mediated hydroazidation of unactivated alkynes has been developed as a new method for the synthesis of vinyl azides. Density functional theory calculations toward this reaction reveal that terminal alkynes with TMS-N3 participated hydroazidation proceed through HN3 formation, deprotonation and silver acetylides formation, nucleophilic addition, and protonation of terminal carbon by AgHCO3. It is also found that water molecules and activation modes of Ag (I) have a significant influence on the title reaction mechanism. Initially, catalyst Ag2CO3 coordinates preferentially with internal N atom of TMS-N3 to assist water as hydrogen source and proton-shuttle in facilitating HN3 formation. Then, the regioselective anti-addition of HN3 to triple bond of active silver-acetylide or ethynyl carbinols affords product vinyl azide via Ag-C σ-bond activation or Ag...C π-coordination activation modes, and the former one is more favorable. The origin of the difference regioselectivity is ascribed to the electronic and orbital effects of the reactive sites. Moreover, Ag2CO3 is the critical catalyst, acting as activator, base, and stabilizer to promote the HN3 and vinyl azide formation. Water molecule plays an important role as proton shuttle to promote HN3 and key active silver acetylides formation, thus improving the yield of product. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The mechanism of the HBr-catalyzed Friedel-Crafts-type reaction between β-naphthol and HCHO was investigated by DFT to improve this reaction. The HBr-H2O co-catalyzed the preferential pathway undergoes the concerted nucleophilic addition and hydrogen shift, stepwise followed by H2O elimination and the CC bond formation. The origin of the high catalytic activity of HBr is ascribed to CH···Br− and OH···Br− interactions, which suggest that the active species is Br−. Moreover, water molecules efficiently assist in improving the activity of Br−. The computational results show that solvent polarity profoundly affects the activation barriers. To our delight, the activation barrier of the rate-determining step for the favored pathway in water is comparable (0.6 kcal/mol difference) with that in acetonitrile. The experimental observation further confirmed our results and demonstrated that the title reaction can be successfully achieved 'on water.' Therefore, we open a new efficient and green strategy for the synthesis of biphenol derivatives. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

DFT calculations were conducted to pursue deeper understandings on the mechanism and the explicit role of trace water in the DBU-catalyzed β-amination of NBS to chalcone. Being different from previously proposed by Liang et al., a cooperative participation of both DBU and water is noticed in the preferred mechanism. The preferential mechanistic scenario assisted by water undergoes three major steps: the formation of succinimide and HBrO, concerted nucleophilic addition and H-shift, and keto-enol tautomerization. Moreover, we found that DBU-HBrO is unnecessary in the third step and three-water-cluster assisted keto-enol tautomerization is the most advantageous case. It is further noted that the catalytic position of the third water molecule and the proton shift orientation to some extent affect step 3 via O···HO and OH···π interactions, which is confirmed by AIM analysis. The computational results suggest that water molecules play pivotal roles as reactant, catalyst, and stabilizer to promote the reaction of chalcone and NBS. The origin of the more stable transition state structure in the rate-determining step of DBU-water catalyzed mechanism is ascribed to noncovalent interactions, halogen bond, and electrostatic interactions than DBU only ones. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The reaction mechanism of ( E)-methyl 3-(2-aminophenyl)acrylate ( A) with phenylisothiocyanate ( B) as well as the vital roles of substrate A and solvent water were investigated under unassisted, water-assisted, substrate A-assisted, and water- A-assisted conditions. The reaction proceeds with four processes via nucleophilic addition, deprotonation and protonation, intramolecular cyclization with hydrogen transfer, and keto-enol tautomerization. According to the different H-shift mode, two possible types of H-shift P1 and P2 are carefully investigated to identify the most preferred pathway, differing in the NH2 group deprotonation and CH group of A protonation processes. It is found that substrate A and water not only act as reactant and solvent, but also as catalyst, proton shuttle, and stabilizer in effectively lowering the energy barrier. Therefore, the results demonstrate that the strong donating and accepting ability of NH2 group on A and the presence of bulk water are the keys to the title reaction proceed. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

DFT investigations are carried out to explore the effective catalyst forms of DBU and H2O and the mechanism for the formation of 2,3-dihydropyrido[2,3- d]-pyrimidin-4(1 H)-ones. Three main pathways are disclosed under unassisted, water-catalyzed, DBU and water cocatalyzed 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 cocatalyzed pathway is the most favored 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]+-H2O 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-H2O. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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 N,N-dimethylformamide (DMF) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) act as not only solvent and nonnucleophilic base, respectively, but also catalysts in the reaction by stabilizing the transition states (TSs) and intermediates via intermolecular hydrogen bonds and electrostatic interactions. Besides, the effective orbital interaction of the reaction site in TS 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. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]