A DFT study of the hydrolysis of hydantoin

Density functional theory (DFT) calculations were made on the hydrolysis of hydantoin (2,4-imidazolidinedione). In the neutral hydrolysis, reacting systems composed of hydantoin and (H₂O)_n with n = 1+3, 2+3, 3+3, and 4+3 were adopted. Three water molecules (“+3”) participate in the in-plane hydrogen-bond circuit, and the n–3 = 1, 2, 3 or 4 water cluster works for the out-of-plane nucleophilic attack onto the carbonyl carbon of hydantoin. Transition states (TSs) involving bond interchanges prompted by proton transfers were determined. The reaction path with n = 3+3 containing N-carbamoyl glycine, N-carboxy glycine and three tetrahedral intermediates was found to be most likely. In the acid-catalyzed hydrolysis, a reacting system composed of hydantoin and H₃O⁺(H₂O)₇ was employed. Ten TSs and nine intermediates were obtained. N-carbamoyl glycine and N-carboxy glycine were confirmed to be detectable stable species. The product consists of glycine, carbonic acid (not CO₂), NH₄⁺, and (H₂O)₅. It has the exothermic energy, whereas the product in the neutral hydrolysis is of the endothermic one for all n values. For both neutral (n = 3+3) and acid-catalyzed hydrolyses, the rate-determining steps were calculated to be for formation of the tetrahedral intermediate, HOOC-CH₂-NH-C(OH)₂NH₂. The pattern of proton transfers along hydrogen bonds was carefully investigated.     

Understanding diastereofacial selection in carbohydrate-based domino cycloadditions: semiempirical and DFT calculations

The sequential cycloaddition of nitroalkenes with methyl vinyl ether was investigated by semiempirical (PM3) and density functional methods (B3LYP/6-31G*). The asymmetric version was also examined with a threoconfigured carbohydrate auxiliary. This produces a larger, more flexible system that complicates the calculation. Most transition structures were then fully optimized at the PM3 level and further refinement was done at ab initio levels. This study represents a model case that enables the rationalization of the high facial selectivity observed in carbohydrate-based nitrone- and nitronate-alkene cycloadditions. The selective endo orientation of the [4+2] pathway results from Coulombic attraction and secondary orbital interactions in the transition state. The stereochemical outcome is largely influenced by a combination of steric shielding from the bulky chiral substituent at C4 and the anomeric effect that places the nitronate C6-alkoxy group in a pseudoaxial arrangement. The resulting conformation favors the subsequent exo approach of methyl vinyl ether to the less hindered re face of the nitronate. It is also remarkable to note that solvation energies stabilize significantly a particular transition structure, thereby explaining the marked stereoselection observed in a polar medium.     

Toward an understanding of the selectivity in domino reactions. A DFT study of the reaction between acetylenedicarboxylic acid and 1, 3-Bis(2-furyl)propane

The mechanism of the domino reaction between acetylenedicarboxylic acid and 1,3-bis(2-furyl)propane has been theoretically studied in the framework of density functional theory. This domino process comprises two consecutive cycloaddition reactions: the first one is initialized by the nucleophilic attack of the C5 position of the furan ring to a conjugate position of acetylenedicarboxylic acid to give a zwitterionic intermediate, which by a subsequent ring-closure process affords an oxanorbornadiene intermediate. The second reaction is an intramolecular concerted cycloaddition of this intermediate to give the final dioxapentacyclic adduct. For the second cycloaddition, which corresponds to the step controlling the selectivity, eight alternative reaction pathways are found. Chemoselectivity, facial selectivity, and stereoselectivity of this domino reaction are related with the different approach modes of the tethered furan to the oxanorbornadiene system of the intermediate. The most favorable pathway takes place along an endo/syn approach of the furan ring relative to the bridged oxygen atom of the oxanorbornadiene system, with participation of the substituted double bond. An analysis of energetic contributions to the potential energy barriers for the intramolecular cycloadditions identifies the different factors controlling the reactive channels. Selectivity outcome is reproduced by these calculations.     

Tautomerism of the antiepileptic drug Felbamate: A DFT study

The Felbamate is a novel anticonvulsant and neuropathic pain drug that can exist as three possible tautomers. Herein, employing density functional theory (DFT) and handling the solvent effects with the PCM model, the structural parameters, energy behavior, natural bond orbital analysis (NBO), as well as the tautomerism of Felbamate are investigated. F1 is the kinetically and thermodynamically most stable tautomer of Felbamate, which contains the amide group in each of the carbamate moieties. The calculated NMR chemical shifts and IR vibrational frequencies are in good agreement with the experimental values, confirming the suitability of the optimized geometry for Felbamate. The tautomerization reaction of F1 to each of the other tautomers occurs via an intramolecular proton transfer. This reaction affects considerably the structural parameters and atomic charges of the Felbamate molecule. A large HOMO-LUMO energy gap implies a high stability of the F1 tautomer.     

A DFT study on the thermal decomposition of 2-chloroethylsilane

Structural Chemistry - The thermal decomposition of 2-chloroethylsilane (H3SiCH2CH2Cl) was investigated by density functional theory (DFT) method at the B3LYP/6-311G(d,p) level. The structures of...     

A DFT study on the vibrational spectroscopy of protoporphyrin IX

Infrared and Raman spectra of protoporphyrin IX were recorded. DFT quantum chemical calculations were performed. Optimised molecular geometry, electric charge distribution, vibrational force constants were computed. The normal coordinate analysis and the scaling of the force constants yielded all the necessary data for the simulation of the infrared and Raman spectra and the potential energy distribution calculations. The result was the interpretation of all vibrational modes of the molecule. Conclusions were drawn from the difficulties arisen during the assignment of the vibrational spectra of such large molecules.     

A DFT study of the ground state of the N3 radical

The X² Π_g ground state of the N₃ radical has been studied by means of the DFT approach with inclusion of nonlocal (gradient) terms. Many different Gaussian basis sets of increasing quality, from small split-shell type up to the TZPP class, have been used. For each of the basis sets, the experimentally known linear symmetric conformation has been optimized using the analytical gradient technique and the vibrational fundamentals have been calculated in the harmonic approximation using the numerical Hessian. For comparison, the standard UHF-type calculations have also been performed. Despite the fact that the Kohn-Sham equations have been resolved in the spin- and symmetryunrestricted manner, the nonlocal version of DFT is able to describe correctly the geometric properties and vibrational spectrum of this open-shell degenerate state, provided that a good quality polarized basis set is used. © 1995 John Wiley & Sons, Inc.     

A DFT study on the microscopic ionization of cysteine in water

The molecular equilibria involved in the second and third macroscopic deprotonation processes of Cys have been theoretically characterized at B3LYP/6-31++G** computing level. The role of solvent was analyzed by using the supermolecule (up to six discrete water molecules), the continuum, and the hybrid supermolecule-continuum models. Also, a novel approach to reveal the solvation effect of the bulk water was employed. Calculations performed with the supermolecule or the Onsager models overestimate absolute pK_as, whereas the PCM continuum model yields data much closer to the experimental values. The supermolecule-PCM approach estimates the pK_a values for the amino group much better than for the thiol group.     

A DFT study of the interaction between microhydrated anions and naphthalendiimides

The characteristics of the interaction of anions with naphthalendiimides, the basic structural motif of a newly synthesized anion channel based on anion···π interactions, are studied by computational methods. Stable complexes are formed with bromide, chloride, fluoride or hydroxide anions, which exhibit strong anion···π interactions in the gas phase. Following the sequence of the polarizing power of the anions, hydroxide and fluoride complexes are the most strongly interacting. The presence of a small number of water molecules strongly affects the anion···π interactions, especially for hydroxide and fluoride complexes, so the differences in interaction strength among the anions drop significantly. The calculations suggest that a small number of water molecules can be crucial to reducing dehydration cost and contributing to stabilizing interactions with the naphthalendiimide units.     

Understanding the mechanism of the intramolecular stetter reaction. A DFT study

The mechanism of the N-heterocyclic carbene (NHC)-catalyzed intramolecular Stetter reaction of salicylaldehyde 1 to yield chromanone 3 has been theoretically studied at the B3LYP/6-31G** level. This NHC-catalyzed reaction takes place through six elementary steps, which involve: (i) formation of the Breslow intermediate IN2; (ii) an intramolecular Michael-Type addition in IN2 to form the new C-C s bond; and (iii) extrusion of the NHC catalyst from the Michael adduct to yield chromanone 3. Analysis of the relative free energies in toluene indicates that while formation of Breslow intermediate IN2 involves the rate-determining step of the catalytic process, the intramolecular Michael-type addition is the stereoselectivity determining step responsible for the configuration of the stereogenic carbon a to the carbonyl of chromanone 3. An ELF analysis at TSs and intermediates involved in the Michael-type addition allows for the characterization of the electronic changes along the C-C bond-formation.     

A DFT study of IRMOF-3 catalysed Knoevenagel condensation

It has been recently reported that IRMOF-3 [Gascon et al., J. Catal, 2009, 261, 75] may behave as a basic catalyst, active in the Knoevenagel condensation. In particular, it has been shown that the basicity of aniline-like amino moieties is enhanced, along with the catalytic activity, when incorporated into MOF structures. The computational study here was aimed at finding possible atomistic explanations of the increased basicity and catalytic activity of the IRMOF-3 embedded aniline groups, experimentally claimed. It was, moreover, aimed at guessing a reaction mechanism for the IRMOF-3 catalysed Knoevenagel condensation of benzaldehyde and ethyl-cyanoacetate. Within the DFT framework we have studied structure and basicity properties of IRMOF-3 and we have analysed the energetics of the catalytic cycle as well as of possible deactivation paths, including it. The increased basicity of IRMOF-3 over other amminic catalysts has been explained via the formation of protonated conjugate derivatives, involving hydrogen-bonds and originating quasi-planar 6-term rings. Several plausible reaction steps have been moreover taken into account and a mechanism for the Knoevenagel condensation, including catalyst deactivation, has been proposed for aniline molecules and embedded aniline moieties. This allowed us to suggest that the increased IRMOF-3 activity, as a basic catalyst, should be mostly related to its water adsorption ability, preserving the properties of the catalytically active amino moieties.     

Hydrolysis of a chlorambucil analogue. A DFT study

We study by density functional theory the hydrolysis of a chlorambucil analogue. Three SN(1) and one SN(2) mechanisms have been compared. Results show that the most likely mechanism involves the formation of an aziridinium ion via a first-order reaction subject to an energy barrier of 24.8 kcal/mol. Additionally, a kinetic study, using the thermodynamic formulation of the Transition State Theory, has been carried out. Theoretical results coincide with experimental values obtained under similar conditions of pH, temperature and chloride concentration.     

A DFT study of ethylene polymerization by zirconocene catalysts

A DFT study of ethylene polymerization by zirconocene catalysts was carried out. Stationary points corresponding to intermediates and transition states were located on the potential energy surface of the [Cp₂ZrC₂H₅]⁺+C₂H₄ model system. Three possible reaction mechanisms involving the formation of β-agostic complexes were considered. The energy and thermodynamic characteristics for different reaction pathways were calculated. Corresponding activation energies lie in the range 3.9–6.8 kcal mol⁻¹. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1168–1177, July, 2000.     

A DFT study of substituent effects in corannulene dimers

Corannulene dimers made up of corannulene monomers with different curvature and substituents were studied using M06-2X, B97D and ωB97XD functionals and 6-31+G* basis set. Corannulene molecules were substituted with five alternating Br, Cl, CH(3), C(2)H or CN units. Geometric results showed that substituents gave rise to small changes in the curvature of corannulene bowls. So, there was not a clear relationship between the curvature of bowls and the changes on interaction energy generated by addition of substituents in the bowl. Electron withdrawing substituents gave rise to a more positive molecular electrostatic potential (MEP) of the bowl, which was able to get a strong interaction with the negative MEP at the surface of a fullerene. Substitution with CN caused the largest effect, giving rise to the most positive MEP and to a large interaction energy of -24.64 kcal mol(-1), at the ωB97XD/6-31+G* level. Dispersive effects must be taken into account to explain the catching ability of the different substituted corannulenes. For unsubstituted dimers, calculations with DFT-D methods employing ωB97XD and B97D functionals led to similar results to those previously reported at the SCS-MP2/cc-pVTZ level for corannulene dimers (A. Sygula and S. Saeb?, Int. J. Quant. Chem., 2009, 109, 65). In particular, the ωB97XD functional led to a difference of only 0.35 kcal mol(-1), regarding MP2 interaction energy for corannulene dimers. On the other hand, the M06-2X functional showed a general considerable underestimation of interaction energies. This functional worked quite well to study trends, but not to obtain absolute interaction energies.     

A gold-catalyzed domino process to the steroid framework

The facile formation of the B and C ring of rac-desoxyequilenin and of a chrysenone derivative in just one preparative step is demonstrated, applying a gold-catalyzed domino process, which involves a benzopyrylium cation as the key intermediate and an intramolecular [3 + 2] cycloaddition as the key step.     

A DFT study of hydride transfers to the carbonyl oxygen of DDQ

Hydride‐transfer reactions between benzylic substrates and 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) were investigated by DFT (density functional theory) calculations. The lowest unoccupied molecular orbital of DDQ has the largest extension on two carbonyl oxygens, which comes from two‐step mixing of antisymmetric orbitals of fragment π MOs. Transition‐state (TS) geometries and activation energies of reactions of four benzylic substrates R²? CH₂‐para‐C₆H₄? R¹ (R¹, R² = H and/or OCH₃) with DDQ were calculated. M06‐2X/6‐311(+*)G* was found to be a practical computational method, giving energies and geometries similar to those of M06‐2X/6‐311++G(3df,2pd) and wB97xD/6‐311++G(3df,2pd). For toluene (R¹ = R² = H), an initiation‐propagation model was suggested, and the calculated kinetic isotope effect k(H)/k(D) = 5.0 with the tunnel correction at the propagating step is in good agreement with the experimental value 5.2. A reaction of para‐MeO? C₆H₄? CH₂(OMe) + DDQ + (H₂O)₁₄ → para‐MeO? C₆H₄? C(?O)H + HOMe + DDQH₂ + (H₂O)₁₃ was investigated by M06‐2X/6‐311(+*)G*. Four elementary processes were found and the hydride transfer (TS1) is the rate‐determining step. The hydride transfer was promoted by association with the water cluster. The size of the water cluster, (H₂O)_n, at TS1 was examined. Three models of n = 14, 20, and 26 were found to give similar activation energies. Metal‐free neutral hydride transfers from activated benzylic substrates to DDQ were proposed to be ready processes both kinetically and thermodynamically. © 2015 Wiley Periodicals, Inc.     

A DFT study on the regioselectivity of the reaction of dichloropropynylborane with isoprene

This theoretical study deals with the reaction of isoprene and dichloropropynylborane. We report the results of the DFT calculations applied to the two processes involved, Diels-Alder cycloaddition and 1,4-alkynylboration. The boron influences both the chemoselectivity and the regioselectivity of this reaction through secondary orbital interactions (SOI hereafter) that give rise to transition structures with strong [4 atom + 3 atom] character. The "meta" regioselectivity observed experimentally for the reaction between 2-substituted 1,3-dienes and alkynyldihaloboranes has been explained as a result of the higher stabilization of these transition structures with "meta" orientation. Intrinsic reaction coordinate calculations were performed to determine connectivities and established the remarkable result that the geometrically very similar transition structures leading to both regioisomeric 1,4-alkynylboration products correspond to different pathways. For the "meta" orientation a direct alkynylboration of the diene through a concerted transition structure was found.