Theoretical insight into the unexpected initial (3 + 2) cycloaddition reaction of mesitonitrile oxide with 1, 4-diazepine derivatives: A computational study.

1,4-Diazepine as an active drug component underlies the potency of most psychotic, anticancer, anticonvulsant, and antibacterial drugs in the market and is, therefore crucial in chemotherapeutic treatment in biomedicine. Proper functionalization of this moiety can afford even more potent drugs. As a result of their therapeutic significance, this study aims at precisely giving a comprehensive computational insight into the unexpected initial reactivity of 1,4-diazepine derivatives and mesitonitrile oxide. The initial reaction between mesitonitrile oxide and 1,4-diazepine derivatives proceeds via a (3 + 2) cycloaddition reaction which leads to the formation of a cycloadduct where the mesitonitrile oxide unexpectedly adds across the imine functionality at the expense of the potential olefinic carbon-carbon double bond. Calculations at the density functional theory (DFT) M06/6-311G (d, p) level of theory indicate that the initial (3 + 2) cycloaddition reaction of mesitonitrile oxide (1,3-dipole) and 1,4-diazepine derivatives (dipolarophile) in all cases proceeds to form the cycloadduct where the 1,3-dipole adds preferentially to the imine functionality at the expense of the potential olefinic carbon-carbon double bond. In light of the parent reaction, the most kinetically favored cycloadductP3A had a rate constant of 5.1 × 106 M-1s-1, which is about 12 manifolds faster than the next competing stereoisomer P1A with a rate constant of 4.1 × 105 M-1s-1 and about 1024 faster than the most favored cycloadduct P3B with a rate constant of 7.2 × 10-19 M-1s-1 in the unfavored pathway (Path B). Irrespective of the electronic and steric nature of the electron-donating (EDG) and electron-withdrawing (EWG) substituents placed on the dipolarophile, the selectivities of the reaction were maintained. Rationalization of the potential energy surface depicts that the 1,3-dipole adds across the dipolarophile via an asynchronous concerted mechanism. Rationalization of the HOMO-LUMO energies of the mesitonitrile oxide (1,3-dipole) and the 1,4-diazepine derivatives (dipolarophile) depict that the EDG-substituted dipolarophile react as nucleophiles, whereas the dipole reacts as an electrophile. Conversely, the HOMO-LUMO interaction between the EWG-substituted dipolarophile indicates that the EWG-substituted dipolarophile react as electrophiles, whereas the dipole reacts as a nucleophile. The electrophilic parr function at various reactive sites of the dipolarophile shows that the 1,3-dipole preferentially adds across the local centers with the largest electrophilic NBO or Mulliken spin densities which is consistent with the energetic trend observed. The reactivity of the 1,4-diazepine derivatives and the mesitonitrile oxide showed poor stereoselectivity.

Exploring the peri- and stereo- selectivities of the cycloaddition reaction of 2-(2- dimethylaminovinyl)-1-benzopyran-4-one with N-phenylmaleimide (NPM) and dimethylacetylenedicarboxylate (DMAD) - A DFT study.

The [4 + 2] cycloaddition reactions of 2-styrylchromones have been predominantly described as one of the efficient methods for the synthesis of xanthones-a prominent class of tricyclic molecules that occur widely in nature. These xanthones are well known for their pharmacological activities especially their role as anti-cancer agents in the medicinal world. In this study, the mechanistic insight into the unusual (peri- and stereo-) selectivities of the reaction of 2-(2-dimethylaminovinyl)-1-benzopyran-4-one (A1) with N-phenylmaleimide (NPM) and dimethylacetylenedicarboxylate (DMAD) has been studied using density functional theory (DFT) at the M06-2X/6-311G (d, p) level of theory. The reaction of A1 and NPM in dimethylformamide (DMF) is periselective towards the initial formation of a [4 + 2] cycloadduct and stereoselectively in an exo fashion with an activation energy of 6.8kcalmol-1 and a rate constant of 6.43×107s-1 which occurs about 878 million times faster than the closest competing pathway for the initial [2 + 2] cycloaddition fashion with an activation energy of 19.0kcalmol-1 and a rate constant of 7.32×10-2s-1. For the substituent effect on the reaction, the reaction selectivity is still maintained where the exo intermediate remains the most kinetically favored cycloadduct. However, the magnitude of the barriers increases slightly with a margin of about 0.1-4.8kcalmol for the electron-donating groups (EDGs) in the order; strong EDGs (OH < NH2 < OCH3) < weak EDGs (

A DFT Mechanistic Study on Base-Catalyzed Cleavage of the ß-O-4 Ether Linkage in Lignin: Implications for Selective Lignin Depolymerization.

The detailed mechanism of the base-catalyzed C-C and C-O bond cleavage of a model compound representing the ß-O-4 linkage in lignin is elucidated using DFT calculations at the M06/6-31G* level of theory. Two types of this linkage have been studied, a C2 type which contains no γ-carbinol group and a C3 type which contains a γ-carbinol. Cleavage of the C2 substrate is seen to proceed via a 6-membered transition structure involving the cation of the base, the hydroxide ion and the α-carbon adjacent to the ether bond. The reaction with KOH has the lowest activation barrier of 6.1 kcal mol-1 with a calculated rate constant of 2.1 × 108 s-1. Cleavage of the C3 substrate is found to proceed via two pathways: an enol-formation pathway and an epoxide-formation pathway. The first path is the thermodynamically favored pathway which is similar to the pathway for the C2 substrate and is the preferred pathway for the isolation of an enol-containing monomer. The second path is the kinetically favored pathway, which proceeds via an 8-membered transition state involving a hydrogen hopping event, and is the preferred pathway for the isolation of an epoxide-containing monomer. The KOH-catalyzed reaction also has the lowest activation barrier of 10.1 kcal mol-1 along the first path and 3.9 kcal mol-1 along the second path, with calculated rate constants of 2.4 × 105s-1 and 8.6 × 109s-1 respectively. Overall, the results provide clarity on the mechanism for the base-catalyzed depolymerization of lignin to phenolic monomers. The results also suggest both NaOH and KOH to be the preferred catalysts for the cleavage of the ß-O-4 linkage in lignin.

CO2 activation and dissociation on the low miller index surfaces of pure and Ni-coated iron metal: a DFT study.

We have used spin polarized density functional theory calculations to perform extensive mechanistic studies of CO2 dissociation into CO and O on the clean Fe(100), (110) and (111) surfaces and on the same surfaces coated by a monolayer of nickel. CO2 chemisorbs on all three bare facets and binds more strongly to the stepped (111) surface than on the open flat (100) and close-packed (110) surfaces, with adsorption energies of -88.7 kJ mol-1, -70.8 kJ mol-1 and -116.8 kJ mol-1 on the (100), (110) and (111) facets, respectively. Compared to the bare Fe surfaces, we found weaker binding of the CO2 molecules on the Ni-deposited surfaces, where the adsorption energies are calculated at +47.2 kJ mol-1, -29.5 kJ mol-1 and -65.0 kJ mol-1 on the Ni-deposited (100), (110) and (111) facets respectively. We have also investigated the thermodynamics and activation energies for CO2 dissociation into CO and O on the bare and Ni-deposited surfaces. Generally, we found that the dissociative adsorption states are thermodynamically preferred over molecular adsorption, with the dissociation most favoured thermodynamically on the close-packed (110) facet. The trends in activation energy barriers were observed to follow that of the trends in surface work functions; consequently, the increased surface work functions observed on the Ni-deposited surfaces resulted in increased dissociation barriers and vice versa. These results suggest that measures to lower the surface work function will kinetically promote the dissociation of CO2 into CO and O, although the instability of the activated CO2 on the Ni-covered surfaces will probably result in CO2 desorption from the nickel-doped iron surfaces, as is also seen on the Fe(110) surface.

A theoretical study of the mechanisms of oxidation of ethylene by manganese oxo complexes.

The mechanisms of oxidation of ethylene by manganese-oxo complexes of the type MnO3L (L = O(-), Cl, CH3, OCH3, Cp, NPH3) have been explored on the singlet, doublet, triplet and quartet potential energy surfaces at the B3LYP/LACVP* level of theory and the results discussed and compared with those of the technetium and rhenium oxo complexes we reported earlier, thereby drawing group trends in the reactions of this important class of oxidation catalysts. In the reactions of MnO3L (L = O(-), Cl(-), CH3, OCH3, Cp, NPH3) with ethylene, it was found that the formation of the dioxylate intermediate along the concerted [3 + 2] addition pathway on the singlet potential energy is favored kinetically and thermodynamically over its formation by a two-step process via the metallaoxetane by [2 + 2] addition. The activation barriers for the formation of the dioxylate and the product stabilities on the singlet PES for the ligands studied are found to follow the order: NPH3 < Cl(-) < CH3O(-) < Cp < O(-) < CH3. On the doublet PES, the activation barriers for the formation of the dioxylate intermediate for the ligands are found to follow the order: CH3O(-) < Cl(-) < Cp < CH3 while the order of product stabilities is: Cl(-) < CH3O(-) < Cp < CH3. The order of dioxylate product stabilities on the triplet surface for the ligands studied is: Cl(-) < CH3O(-) < Cp < CH3 < NPH3 < O(-) and the order on the quartet surface is O(-) < Cp < CH3 < NPH3 < Cl(-) < CH3O(-). The re-arrangement of the metallaoxetane intermediate to the dioxylate is not a feasible reaction for all the ligands studied. Of the group VII B metal oxo complexes studied, MnO4(-) and MnO3(OCH3) appear to be the best catalysts for the exclusive formation of the dioxylate intermediate, MnO3(OCH3) being better so on both kinetic and thermodynamic grounds. The best epoxidation catalyst for the Mn complexes is MnO3Cl; the formation of the epoxide precursor will not result from the reaction of LMnO3 (L = O(-), Cp) with ethylene on any of the surfaces studied. The trends observed for the oxidation reactions of the Mn complexes with ethylene compare closely with those reported by us for the ReO3L and TcO3L (L = O(-), Cl, CH3, OCH3, Cp, NPH3) complexes, but there is far greater similarity between the Re and Tc complexes than between Mn and either of the other two. There does not appear to be any singlet-triplet or doublet-quartet spin-crossover in any of the pathways studied.

A density functional theory study of the mechanisms of oxidation of ethylene by rhenium oxide complexes.

The oxo complexes of group VII B are of great interest for their potential toward epoxidation and dihydroxylation. In this work, the mechanisms of oxidation of ethylene by rhenium-oxo complexes of the type LReO3 (L = O(-), Cl, CH3, OCH3, Cp, NPH3) have been explored at the B3LYP/LACVP* level of theory. The activation barriers and reaction energies for the stepwise and concerted addition pathways involving multiple spin states have been computed. In the reaction of LReO3 (L = O(-), Cl, CH3, OCH3, Cp, NPH3) with ethylene, it was found that the concerted [3 + 2] addition pathway on the singlet potential energy surfaces leading to the formation of a dioxylate intermediate is favored over the [2 + 2] addition pathway leading to the formation of a metallaoxetane intermediate and its re-arrangement to form the dioxylate. The activation barrier for the formation of the dioxylate on the singlet PES for the ligands studied is found to follow the order O(-) > CH3 > NPH3 > CH3O(-) > Cl(-) > Cp and the reaction energies follow the order CH3 > O(-) > NPH3 > CH3O(-) > Cl(-) > Cp. On the doublet PES, the [2 + 2] addition leading to the formation the metallaoxetane intermediate is favored over dioxylate formation for the ligands L = CH3, CH3O(-), Cl(-). The activation barriers for the formation of the metallaoxetane intermediate are found to increase for the ligands in the order CH3 < Cl(-) < CH3O(-) while the reaction energies follow the order Cl(-) < CH3O(-) < CH3. The subsequent re-arrangement of the metallaoxetane intermediate to the dioxylate is only feasible in the case of ReO3(OCH3). Of all the complexes studied, the best dioxylating catalyst is ReO3Cp (singlet surface); the best epoxidation catalyst is ReO3Cl (singlet surface); and the best metallaoxetane formation catalyst is ReO3(NPH3) (triplet surface).

Density functional theory study of the mechanisms of oxidation of ethylene by chromyl chloride.

The mechanistic pathways for the formation of epoxide, 1,2-dichloroethane, 1,2-chlorohydrin, acetaldehyde, and vinyl alcohol precursors in the oxidation of ethylene by chromyl chloride has been studied using hybrid density functional theory at the B3LYP/LACVP* level of theory. The formation of the epoxide precursor (Cl(2)(O)Cr-OC(2)H(4)) was found to take place via initial [2 + 2] addition of ethylene across the Cr=O bonds of CrO(2)Cl(2) to form a chromaoxetane intermediate. The pathway involving initial [3 + 2] addition of ethylene to the oxygen and chlorine atoms of CrO(2)Cl(2), which has not been explored in earlier studies, was found to be favored over [3 + 2] addition of olefin to two oxygen atoms of CrO(2)Cl(2). The formation of the 1,2-dichloroethane precursor, which was found to take place via [3 + 2] addition of ethylene to two chlorine atoms of CrO(2)Cl(2), is slightly favored over the formation of the epoxide precursor. The 1,2-chlorohydrin precursor has been found to originate from [3 + 2] addition of ethylene to the oxygen and chlorine atoms of CrO(2)Cl(2) as opposed to [2 + 2] addition of ethylene to the Cr-Cl bond. The vinyl alcohol precursor O=CrCl(2)-(OH)CH=CH(2) has been found to exist only on the triplet potential energy surface. The acetaldehyde precursor (O=CrCl(2)-OCHCH(3)) was found to be the most stable species on the reaction surface. Hydrolysis may be required to generate the epoxide, 1,2-dichloroethane and 1,2-chlorohydrin from the respective precursors.