Computational Studies of Nucleophilic Substitution at Nitrogen Center: Reactions of NH2Cl with HO-, CH3O- and C2H5O.

The atomic-level mechanisms of the nucleophilic substitution reactions at the nitrogen center (SN2@N) were investigated for the reactions of chloramine (NH2Cl) with the alkoxide ions (RO-, where R=H, CH3, and C2H5) using DFT and MP2 methods. The computed potential energy profiles for the SN2@N pathways involving the back-side attack of the nucleophiles show the typical double-well potential with submerged barriers similar to the SN2 reactions at the carbon center (SN2@C). However, the pre-reaction and post-reaction complexes are, respectively, the N-H⋅⋅⋅O and N-H⋅⋅⋅Cl hydrogen-bonded intermediates, which are different from those generally seen in SN2@C reactions. The SN2@N pathways involving front-side attack of the nucleophiles have high-energy barriers. The potential energy surfaces (PESs) along the proton-transfer pathways were flat. In addition to the proton-transfer and SN2 pathways, we also observed a new path for the methoxide and ethoxide nucleophiles where a hydride-transfer from the nucleophile to chloramine resulted in the products Cl-+R'CHO+NH3, (R'=H, CH3), and was the most exoergic. A comparison of the energetics obtained used different DFT and MP2 methods with that of the benchmark coupled-cluster methods reveals that CAM-B3LYP best describes the PESs.

Inelastic scattering of formaldehyde on Au(111) surface.

Inelastic scattering between gas molecules and surfaces is a fundamental process that has been investigated extensively. In recent gas-surface scattering experiments [Phys. Chem. Chem. Phys. 19, 19904 (2017)] on formaldehyde scattering off the gold surface, the scattered formaldehyde molecules had a high propensity to excite twirling motion about the C-O bond. In the work presented here, we used classical dynamics simulations to understand energy transfer in formaldehyde-surface collisions and to probe the mechanism of interconversion of translational energy to rotational energy. The simulations reveal an increase in the rotational energy distribution with an increase in collision energies and a preferential rotational excitation about the C-O bond consistent with the experiments. The high propensity to excite the twirling motion was found to arise from a steering motion about the C-O bond during the scattering process governed by the minimum energy path.

Coordination and Stabilization of a Lithium Ion with a Silylene.

Herein, we report the stabilization of lithium-ion as the source of lithium to use as a trans-metalation reagent [{PhC(Nt Bu)2 Si(t Bu)Li}2 I(t BuN)2 CPh] (1). The reaction of 3 equivalents of the LSit Bu (L=PhC(Nt Bu)2 ) and lithium iodide at low temperature leads to a silylene stabilized lithium-ion with an additional coordination of amidinate ligand. Compound 1 shows two four membered and one six membered ring as confirmed by QTAIM calculations. Whereas the reaction of the LSiCl with 1.5 equivalents of carbodiimide (CyN)2 C at room temperature affords compound [PhC(Nt Bu)2 Si(Cl)(NCy)2 NCy] (2) with the CN2 SiN2 C skeleton containing silicon as a central atom. Both the compounds were fully characterized by NMR, mass spectrometry, X-ray crystallographic analysis, and quantum mechanical calculations.

[2+4] Cycloaddition Product of an Amidinate Substituted Dialumene with Toluene.

Reduction of LAlI2 (L=PhC(Ni Pr2 C6 H3 )2 ) with two equivalents of KC8 in toluene affords the [2+4]cycloaddition product of a dialumene with toluene. The mechanism for the formation of product complex was investigated using density functional theory (DFT) methods.

E-Z Isomerization in Guanidine: Second-order Saddle Dynamics, Non-statisticality, and Time-frequency Analysis.

Our recent work on the E-Z isomerization reaction of guanidine using ab initio chemical dynamics simulations [Rashmi et al., Regul. Chaotic Dyn. 2021, 26, 119] emphasized the role of second-order saddle (SOS) in the isomerization reaction; however, we could not unequivocally establish the non-statistical nature of the dynamics followed in the reaction. In the present study, we performed thousands of on-the-fly trajectories using forces computed at the MNDO level to investigate the influence of second-order saddle in the E-Z isomerization reaction of guanidine and the role of intramolecular vibrational energy redistribution (IVR) on the reaction dynamics. The simulations reveal that while majority of the trajectories follow the traditional transition state pathways, 15 % of the trajectories follow the SOS path. The dynamics was found to be highly non-statistical with the survival probabilities of the reactants showing large deviations from those obtained within the RRKM assumptions. In addition, a detailed analysis of the dynamics using time-dependent frequencies and the frequency ratio spaces reveal the existence of multiple resonance junctions that indicate the existence of regular dynamics and long-lived quasi-periodic trajectories in the phase space associated with non-RRKM behavior.

Dodging the Conventional Reactivity of o-Alkynylanilines under Gold Catalysis for Distal 7-endo-dig Cyclization.

A direct ring-closing strategy involving a less facile 7-endo-dig carbacyclization of o-alkynylaniline derivatives for the synthesis of benzo[b]azepines has been presented. The trivial well-documented 5-endo-dig cyclization in o-alkynylaniline derivatives due to high nucleophilicity of nitrogen has been overcome by using their vinylogous amides under gold catalysis to access a wide array of benzo[b]azepines in an atom economical way with excellent functional group compatibility. Deuterium scrambling experiments and DFT studies favor a mechanism involving stabilizing conformational change of the initially formed seven-membered vinyl gold intermediate through a key cyclopropyl gold carbene intermediate and its subsequent protodeauration mediated by the counter anion.

Influence of second-order saddles on reaction mechanisms.

The transition state, a first-order saddle point on the potential energy surface, plays a central role in understanding the mechanism, dynamics, and rate of chemical reactions. However, we recently identified energetically accessible second-order saddles (SOS) in certain reactions and showed that the SOS plays a crucial role in the dynamics of the reactions [Pradhan et al., Phys. Chem. Chem. Phys., 2019, 21, 12837; Rashmi et al., Regul. Chaotic Dyn., 2021, 26, 119]. In the present work, we investigated the role of second-order saddle points on the dynamics of the thermal denitrogenation of 1-pyrazoline using ab initio classical trajectory simulations at the CASSCF(4,4)/6-31+G* level of theory, for total energies of 130, 140, and 150 kcal mol-1 available to the system. In this unimolecular dissociation reaction, the SOS point is 4 kcal mol-1 higher in energy than the synchronous bond-breaking transition state and opens up an additional reaction pathway. We found that the fraction of molecules following the synchronous bond-breaking pathway decreased with an increase in the total available energy in the reaction, accompanied by an increase in the fraction following the asynchronous pathway. To further understand the competition between the transition state and the SOS pathways, we investigated the mechanism of halogen-substituted 1-pyrazolines where the SOS energies are comparable to that of the transition states.

Dynamics of a gas-phase SNAr reaction: non-concerted mechanism despite the Meisenheimer complex being a transition state.

The commonly accepted mechanism of the nucleophilic aromatic substitution (SNAr) reaction has been found to be governed by the nature of the Meisenheimer structure on the potential energy surface. A stable Meisenheimer intermediate favors a stepwise mechanism, while a Meisenheimer transition state favors a concerted mechanism. Here, we show by using a detailed potential energy map (using the DFT and DLPNO-CCSD(T)/CBS methods) and ab initio classical trajectory simulations that the F- + C6H5NO2 SNAr reaction involves a Meisenheimer transition state and follows a stepwise mechanism in contrast to the expected concerted pathway. The stepwise mechanism observed in the trajectory simulations takes place by the formation of various ion-dipole and σ-complexes. While the majority of the trajectories follow the multi-step mechanism and avoid the minimum energy path, a considerable fraction exhibit a roaming atom mechanism where the F atom hovers around the phenyl ring before the formation of the products.

Transition between [R]- and [S]-stereoisomers without bond breaking.

The fifty-year old proposal of a nondissociative racemization reaction of a tetracoordinated tetrahedral center from one enantiomer to another via a planar transition state by Hoffmann and coworkers has been explored by many research groups over the past five decades. A number of stable molecules with planar tetracoordinated and higher-coordinated centers have been designed and experimentally realized; however, there has not been a single example of a molecular system that can possibly undergo such racemization. Here we show examples of molecular species that undergo inversion of stereochemistry around tetrahedral centers (Si, Al- and P+) either via a planar transition state or an intermediate state using quantum mechanical, ab initio quasi-classical dynamics calculations, and Born-Oppenheimer molecular dynamics (BOMD) simulations. This work is expected to provide potential leads for future studies on this fundamental phenomenon in chemistry.

Can reactions follow non-traditional second-order saddle pathways avoiding transition states?

We report here an ab initio (CASSCF/6-31+G*) trajectory simulation study on the mechanisms of the denitrogenation of 1-pyrazoline and its subsituted analogue that reveals reaction pathways via a high energy second-order saddle (SOS) region. This mechanism involves the molecule adopting a five-membered planar structure contrary to the traditional boat-like transition state. The SOS offers a trifurcation point where a pathway branches into three, different from the single pathway associated with a transitions state. We observe that the molecules following the SOS path exhibit distinctive dynamical features and form products with high translational energies and low rotational energies compared to those following the traditional pathways. In addition, the SOS pathway provides an alternative mechanism for the formation of stereo-selective products. Interestingly, although the reaction proceeds via a trimethylene diradical intermediate, the simulations show that the product cyclopropane is formed with a major single inversion of the configuration consistent with experimental observations. They also reveal mechanisms that do not follow the minimum energy paths and exhibit non-statistical dissociation dynamics.

Theoretical investigation of the isomerization pathways of diazenes: torsion vs. inversion.

Diazenes are an important family of organic compounds used widely in synthetic and materials chemistry. These molecules have a planar geometry and exhibit cis-trans isomerization. The simplest of all these molecules - diazene (N2H2) - has been subjected to several experimental and theoretical studies. Two mechanisms have been proposed for the cis-trans isomerization of diazene, which are an in-plane inversion and an out-of-plane torsion. The activation energies for these pathways are similar and the competition between these two mechanisms has been discussed in the literature based on electronic structure theory calculations. Three decades ago, a classical dynamics investigation of diazene isomerization was carried out using a model Hamiltonian and it was indicated that the in-plane inversion is forbidden classically because of a centrifugal barrier and the out-of-plane torsion is the only isomerization pathway. In the present work, we investigated the cis-trans isomerization dynamics of diazene using ab initio classical trajectory simulations at the CASSCF(2,2)/aug-cc-pVDZ level of electronic structure theory. The simulation results confirmed the presence of the aforementioned centrifugal barrier for the inversion and torsion was the only observed pathway. The calculations were repeated for a similar system (difluorodiazene, N2F2) and again the centrifugal barrier prevented the inversion pathway.

Quantum chemical investigation of the thermal denitrogenation of 1-pyrazoline.

Understanding the mechanism of the denitrogenation of 1-pyrazolines is of fundamental importance due to the unusual stereochemical preferences (major single inversion) seen in the product formation. In the present work, a detailed investigation on the mechanisms of the thermal denitrogenation of 1-pyrazoline was undertaken using CASSCF and CASPT2 methods with 6-31+G*, 6-311+G*, cc-pVDZ, cc-pVTZ, and aug-cc-pVDZ basis sets. The CASSCF calculations were performed with a series of different active spaces. It was found that the energetics obtained from CASSCF(4,4), where the σ,σ* orbitals of both the C-N bonds were included in the active space, are similar to those obtained using the (12,12) active space. The CASSCF(4,4) energetics were found to remain unaffected with the increase in the basis sets. Three different denitrogenation paths were obtained: (1) a synchronous path where a simultaneous breaking of both the C-N bonds leads to a planar trimethylene diradical intermediate, (2) an asynchronous concerted path which involves the unsymmetrical breaking of C-N σ bonds resulting in single inverted cyclopropane formation, and (3) an asynchronous step-wise path which involves the unsymmetrical breaking of the C-N bonds leading to diazenyl diradical intermediates. The barrier for the synchronous denitrogenation path was found to be lower in energy than that of the asynchronous paths. To check the applicability of the DFT and MP2 methods for this reaction, the potential energy profiles were mapped using different DFT functionals (B3LYP, B2PLYP, M06-2X) and the MP2 method. However, the DFT and MP2 methods failed to provide a correct description of the potential energy surface in the diradical regions.

Classical Dynamics Simulations of Dissociation of Protonated Tryptophan in the Gas Phase.

Gas phase decomposition of protonated amino acids are of great interest due to their role in understanding protein and peptide chemistry. Several experimental and theoretical studies have been reported in the literature on this subject. In the present work, decomposition of the aromatic amino acid protonated tryptophan was studied by on-the-fly classical chemical dynamics simulations using density functional theory. Mass spectrometry and electronic structure theory studies have shown multiple dissociation pathways for this biologically relevant molecule. Unlike aliphatic amino acids, protonated tryptophan dissociates via NH3 elimination rather than the usual iminium ion formation by combined removal of H2O and CO molecules. Also, a major fragmentation pathway in the present work involves Cα-Cß bond fission. Results of the chemical dynamics simulations reported here are in overall agreement with experiments, and detailed atomic level mechanisms are presented.

Time-Dependent Density Functional Theoretical Investigation of Photoinduced Excited-State Intramolecular Dual Proton Transfer in Diformyl Dipyrromethanes.

In recent research [ Chem. Commun. 2014 , 50 , 8667 ], it was found that photoinduced enolization occurred in 1,9-diformyl-5,5-diaryldipyrromethane (DAKK) by excited-state dual proton transfer resulting in a red-shifted absorption, a phenomena not observed in 1,9-diformyl-5,5-dimethyldipyrromethane (DMKK) and 1,9-diformyl-5-aryldipyrromethane (MAKK). The observation was supported by preliminary density functional theoretical (DFT) calculations. In the work reported here, a detailed and systematic study was undertaken considering four molecules, 1,9-diformyldipyrromethane (DHKK), DMKK, MAKK, and DAKK and their rotational isomers using DFT methods. Different processes, namely, cis-trans isomerization and single and double proton transfer processes, and their mechanistic details were investigated in the ground and excited states. From the simulation studies, it was seen that the presence of different substituents at the meso carbon does not affect the λabs values during cis → trans isomerization. However, enolization by proton transfer processes were found to be influenced by the substituents, as seen in the experiments. Enolization was observed to follow a stepwise mechanism, that is, diketo → monoenol → dienol. While monoenols showed negligible substituent effects on the λabs values, a large red shift in λabs was seen only in DAKK, in agreement with the experimental findings. This observation can be attributed to the lowering of the keto → enol activation barrier, stabilization of DAEE in the S1 state, and the charge transfer nature of the transitions involved in DAEE.

Mechanisms and dynamics of protonation and lithiation of ferrocene.

By elucidating the mechanism of the simplest electrophilic substitution reaction of ferrocene, it was found that the verification of the protonation reaction has been a difficulty. In the work reported here, ab initio chemical dynamics simulations were performed at B3LYP/DZVP level of theory to understand the atomic level mechanisms of protonation and lithiation of ferrocene. Protonation of ferrocene resulted in the agostic and metal-protonated forms. Trajectory calculations revealed that protonation of ferrocene occurs by exo and endo mechanisms, with exo being the major path. H(+) was found to be mobile and hopped from the Cp ring to the metal center and vice versa after the initial attack on ferrocene, with the metal-complex having a shorter lifetime. These results remove the ambiguity surrounding the mechanism, as proposed in earlier experimental and computational studies. Lithiation of ferrocene resulted in the formation of cation-π and metal-lithiated complexes. Similar to protonation, trajectory results revealed that both exo and endo paths were followed, with the exo path being the major one. In addition, lithiated-ferrocene exhibited planetary motion. The major path (exo) followed in the protonation and lithiation of ferrocene is consistent with the observations in earlier experimental studies for other hard electrophiles.

Phosphasilene mediated CO activation and deoxygenative homo coupling of CO molecules in reactions with metal carbonyls.

Herein, we report the synthesis of a new sterically demanding hyper-coordinate phosphasilene (Mes*PSi(SiMe3)(PhC(N t Bu)2) (1) and its unprecedented reactivity with metal carbonyls (M = Fe, Mo, W). The reaction of 1 with Fe(CO)5 involves the deoxygenative homocoupling of two CO molecules, forming a rare ketene (µ-CCO) inserted Fe complex 2. Contrastingly, reactions with M(CO)6 (M = Mo, W) entail the deoxygenated activation of one CO molecule, with the second CO molecule being trapped between Si and P atoms. All the compounds including their crystal structures, are thoroughly characterized and potential energy profiles for the reaction mechanisms are also explored.

Modeling the formaldehyde-graphene interaction using a formaldehyde-pyrene system.

Study of the dynamics of H2CO confined within graphene sheets and sensing of H2CO by graphene require an analytic representation of the intermolecular potential between H2CO and graphene. To develop an intermolecular potential for H2CO interacting with graphene, ab initio calculations were performed at the MP2/MG3S, B97-D/MG3S and LPNO-CEPA/1/CBS levels of theory using H2CO-pyrene as a model. The intermolecular interactions were computed for three different orientations of formaldehyde approaching pyrene for a complete description of the interaction. The interaction energy obtained from the MP2, B97-D and LPNO-CEPA/1 methods were compared with the CCSD(T) method. The LPNO-CEPA/1/CBS method gives the best interaction energies compared to the CCSD(T)/CBS method. The LPNO-CEPA/1/CBS data obtained is fitted to an analytical potential energy function written as the sum of two-body interactions between the C atoms of pyrene and the C, H, O atoms of formaldehyde. The fitted potential energy function represents the ab initio data in excellent agreement for all the orientations considered. The analytical potential was also found to represent very well the interactions for two new orientations not considered in fitting, emphasizing the global nature of the analytic potential. The new potential is also compared with the van der Waals AMBER model.

Simulation studies of the Cl- + CH3I SN2 nucleophilic substitution reaction: comparison with ion imaging experiments.

In the previous work of Mikosch et al. [Science 319, 183 (2008)], ion imaging experiments were used to study the Cl(-) + CH3I → ClCH3 + I(-) reaction at collision energies E(rel) of 0.39, 0.76, 1.07, and 1.9 eV. For the work reported here MP2(fc)/ECP/d direct dynamics simulations were performed to obtain an atomistic understanding of the experiments. There is good agreement with the experimental product energy and scattering angle distributions for the highest three E(rel), and at these energies 80% or more of the reaction is direct, primarily occurring by a rebound mechanism with backward scattering. At 0.76 eV there is a small indirect component, with isotropic scattering, involving formation of the pre- and post-reaction complexes. All of the reaction is direct at 1.07 eV. Increasing E(rel) to 1.9 eV opens up a new indirect pathway, the roundabout mechanism. The product energy is primarily partitioned into relative translation for the direct reactions, but to CH3Cl internal energy for the indirect reactions. The roundabout mechanism transfers substantial energy to CH3Cl rotation. At E(rel) = 0.39 eV both the experimental product energy partitioning and scattering are statistical, suggesting the reaction is primarily indirect with formation of the pre- and post-reaction complexes. However, neither MP2 nor BhandH/ECP/d simulations agree with experiment and, instead, give reaction dominated by direct processes as found for the higher collision energies. Decreasing the simulation E(rel) to 0.20 eV results in product energy partitioning and scattering which agree with the 0.39 eV experiment. The sharp transition from a dominant direct to indirect reaction as E(rel) is lowered from 0.39 to 0.20 eV is striking. The lack of agreement between the simulations and experiment for E(rel) = 0.39 eV may result from a distribution of collision energies in the experiment and/or a shortcoming in both the MP2 and BhandH simulations. Increasing the reactant rotational temperature from 75 to 300 K for the 1.9 eV collisions, results in more rotational energy in the CH3Cl product and a larger fraction of roundabout trajectories. Even though a ClCH3-I(-) post-reaction complex is not formed and the mechanistic dynamics are not statistical, the roundabout mechanism gives product energy partitioning in approximate agreement with phase space theory.