Double Hydrogen Transfer Research Articles

Efficient Synthesis of a C2-Symmetric 2,2'-Bipyridine-α,α'-1-t-butyl-diol Ligand by Stereoselective Double Hydrogen Transfer to a 2,2'-Bipyridine-diketone.

An efficient and practical method was developed for the synthesis of C2-symmetric 2,2'-bipyridine-α,α'-1-t-butyl-diol ligands. The disclosed synthesis involves the Ullmann homocoupling of a keto bromo-pyridine under NiCl2/Zn/PPh3 conditions, followed by the stereoselective double hydrogen transfer to the obtained 2,2'-bipyridine-diketone using RuII Noyori-Ikariya catalysts. This approach allowed the successful synthesis of 2,2'-bipyridine-α,α'-1-t-butyl-diol, i.e (S,S)-Bolm's ligand, with a quantitative yield and an excellent stereoselectivity (ee>99.5 %, de>99.5 %), with an overall yield of 69 % from easily accessible starting materials.

Theoretical predictions on In-Plane aromaticity in double hydrogen transfer reactions between ethane and ethylene

Aromaticity, traditionally understood as a cornerstone concept elucidating the stability, reactivity, and structure of unsaturated organic compounds, has evolved to encompass inorganic molecules, saturated systems with delocalized electrons, and, significantly, transition structures. Our research delves into the exploration of in-plane aromaticity within the transition state (TS) of the Double Hydrogen Transfer reaction (DHTR) between ethylene and ethane, marking a novel approach to understanding cyclic reaction mechanisms. Through the application of density functional theory and verification via the Gaussian09 program’s intrinsic reaction coordinate analysis, our investigation assesses parameters such as aromatic nucleus-independent chemical shift (NICS) and Mayer bond orders to characterize the TS. The findings reveal a distinctly synchronous in-plane aromatic TS, highlighting its aromatic features. This research paves the way for future studies aimed at unravelling the influence of aromaticity on the kinetics and pathways of similar reactions, enhancing our grasp of its pivotal role in chemical processes.

Synthesis of Dihydroquinoxalinones from Biomass-Derived Keto Acids and o-Phenylenediamines.

A novel catalyst-free cascade amination/cyclization/reduction reaction was developed for the synthesis of various Dihydroquinoxalinones under mild conditions from accessible biomass-derived keto acids and 1,2-phenylenediamines with ammonia borane as a hydrogen donor. This single-step approach enables a simple and eco-friendly route toward the direct synthesis of 12 kinds of Dihydroquinoxalinones in moderate to excellent yields in the green solvent dimethyl carbonate. The results of deuterium-labeling experiments and density function calculations demonstrate that the reductive process proceeds along a double hydrogen transfer pathway. An acceptable yield of Dihydroquinoxalinone can be afforded in a gram-scale experiment, illustrating the practicality of the as-reported reaction system.

Nuclear Quantum Effects in Proton or Hydrogen Transfer.

Proton or hydrogen transfers, basic chemical reactions, proceed either by thermally activated barrier crossing or via tunneling. Studies of molecules undergoing single or double proton or hydrogen transfer in the ground or excited electronic state reveal that tunneling can dominate under conditions usually considered to favor the thermal process. Moreover, the tunneling probability strongly varies for excitation of certain vibrational modes, which changes the effective barrier and/or proton transfer distance. When the reaction is fast compared to vibrational relaxation, the mode selectivity can still be maintained for molecules in solutions at 293 K. These observations point to dangers of relating the calculated minimum energy paths and the associated barriers to the experimentally obtained activation energies. The multidimensional character of the reaction coordinate is obvious; it can dramatically change for slowly and rapidly relaxing environments. We postulate that the hydrogen bond definition should be extended by specifically including the role of molecular vibrations.

Computationally aided design of defect-appended aliphatic amines for CO2 activation within UiO-66.

The introduction of aliphatic amine groups in metal-organic frameworks (MOFs) can improve their ability to capture CO2 at low pressures, driven by chemisorptive formation of C-N bonds. Understanding the chemistry of amine-CO2 interaction within the confined porous space in MOFs is key to design and develop effective CO2 adsorbents. Here, we report a computational study of CO2 adsorption and subsequent formation of carbamic acid within defective UiO-66 functionalised with a series of four amino acids of varying aliphatic chain length (glycine, beta-alanine, gamma-aminobutyric acid and 5-aminovaleric acid). Periodic density functional theory (DFT) calculations suggest that CO2 can be activated by the aliphatic amines only when they are sufficiently close to each other to form hydrogen bonds and stabilise the adduct with CO2, a condition met only by UiO-66 functionalised with gamma-aminobutyric acid and 5-aminovaleric acid. The proposed mechanism involves the formation of a carbamate zwitterionic intermediate, which evolves via a simultaneous double hydrogen transfer with a proximal amine group to a carbamic acid. For the 5-aminovaleric acid case, it is suggested that even the functionalisation of just 16% of the available defective sites can be sufficient to form the CO2-amine adduct. Finally, we also investigate the effect of a possible protonation of the amine groups by the hydroxyl groups in the clusters, finding that this could lead to even more favourable interaction with CO2.

Quantum dynamics calculations on isotope effects of hydrogen transfer isomerization in formic acid dimer

We present a quantum dynamics study on the isotope effects of hydrogen transfer isomerization in the formic acid dimer, and this is achieved by multidimensional dynamics calculations with an efficient quantum mechanical theoretical scheme developed by our group, on a full-dimensional neural network ab initio potential energy surface. The ground-state and fundamental tunneling splittings for four deuterium isotopologues of formic acid dimer are considered, and the calculated results are in very good general agreement with the available experimental measurements. Strong isotope effects are revealed, the mode-specific fundamental excitation effects on the tunneling rate are evidently influenced by the deuterium substitution of H atom with the substitution on the OH bond being more effective than on the CH bond. Our studies are helpful for acquiring a better understanding of isotope effects in the double-hydrogen transfer processes.

Solvent effects on direct and indirect tautomerism of pyrimidin‐2(1H)‐one/pyrimidin‐2‐ol

AbstractA theoretical study at the B3LYP/6‐311++G(d,p) level on tautomeric conversion of pyrimidin‐2(1H)‐one (PYH) to pyrimidin‐2‐ol (PY) was performed. Two mechanisms have been considered for this processes: (i) one in which the hydrogen is directly transferred, mechanisms A, through TS12 and (ii) another one in which a double hydrogen transfer takes place via TS1122, by formation of the corresponding dimer, mechanisms B. The results associated with the gas phase reveal that overcame to TS12 needs high activation free energies of 34.47 kcal/mol, as a consequence of the strain associated with the formation of the four‐membered transition state, while overcame to TS1122 requires much lower activation free energies, 4.97 kcal/mol. The effect of solvent on the studied tautomerization in implicit, explicit, and a combination of both implicit and explicit solvation models in various media (protic and aprotic polar solvents) has been considered. The results show that the use of a protic polar solvent reduces the energy barrier of the corresponding transition states in a very significant amount.

Gas-phase amination of aromatic hydrocarbons by corona discharge-assisted nitrogen fixation

This paper reports on the gas-phase amination reaction of aromatic hydrocarbons occurring under corona discharge conditions with N2 gas as the nitrogen source. The corona discharge device within an atmospheric pressure chemical ionization source was employed to achieve the plasma-assisted N2 fixation, and the coupled ion trap mass spectrometer (IT-MS) was used to detect positively charged product ions. In the model case, under APCI conditions, unusual product ions, [M + 16]+ and [M + 14]+, were observed. Based on the high resolution MS data and tandem mass spectrometric information, [M + 16]+ was confirmed to be protonated p-toluidine and [M + 14]+ was confirmed to be p-methylphenylnitrenium ion. According to the experimental results of the isotopic labelling and substituent effect, one feasible mechanism is proposed as follows. Firstly, N2 is activated by plasma caused via the corona discharge and then electrophilically attacks toluene, yielding the key intermediate, p-methylphenylnitrenium; secondly, the intermediate undergoes double-hydrogen transfer reaction to give rise to the final product ion, protonated p-toluidine. This study may provide a novel idea to explore new and green method for the synthesis of anilines.

Double intramolecular hydrogen transfer assisted dual emission in a carbazole-embedded porphyrin-like macrocycle.

The introduction of a pyrrole ring at one of the meso positions of carbazole-based porphyrins lowers the structural symmetry and results in dual emission, which strongly depends on the excitation wavelength and temperature. The origin of dual emission induced by NH-tautomerism is confirmed via photophysical and DFT calculations.

Multidimensional Hydrogen Tunneling in Supported Molecular Switches: The Role of Surface Interactions.

The nuclear tunneling crossover temperature (T_{c}) of hydrogen transfer reactions in supported molecular-switch architectures can lie close to room temperature. This calls for the inclusion of nuclear quantum effects (NQEs) in the calculation of reaction rates even at high temperatures. However, computations of NQEs relying on standard parametrized dimensionality-reduced models quickly become inadequate in these environments. In this Letter, we study the paradigmatic molecular switch based on porphycene molecules adsorbed on metallic surfaces with full-dimensional calculations that combine density-functional theory for the electrons with the semiclassical ring-polymer instanton approximation for the nuclei. We show that the double intramolecular hydrogen transfer (DHT) rate can be enhanced by orders of magnitude due to surface fluctuations in the deep-tunneling regime. We also explain the origin of an Arrhenius temperature dependence of the rate below T_{c} and why this dependence differs at different surfaces. We propose a simple model to rationalize the temperature dependence of DHT rates spanning diverse fcc [110] surfaces.

Fluorinated Porphycenes: Synthesis, Spectroscopy, Photophysics, and Tautomerism.

Six porphycenes have been synthesized, bearing one, two, or three fluorine atoms attached directly to the 18-π-electron system at the meso positions. These novel compounds have been characterized by structural, electrochemical, and spectral techniques, combined with quantum chemical calculations. In three fluoroporphycenes, the unsymmetric substitution pattern leads to the presence of two nonequivalent trans tautomeric forms. They have been identified using electronic absorption, emission, and magnetic circular dichroism spectroscopies. Their relative energies have been estimated for the ground and lowest excited electronic states. Tautomerization potential is quasi-symmetric in S0 , but becomes strongly nonsymmetric in S1 . Femtosecond transient absorption studies allowed determination of tautomerization rates, larger and similar for both directions of the double hydrogen transfer in S0 , lower and disparate in S1 . Fluoroporphycenes emerge as good candidates for detailed studies of mechanisms of double hydrogen transfer, as well as processes responsible for rapid radiationless excited state depopulation.

Dioxygen Activation by Internally Aromatic Metallacycle: Crystallographic Structure and Mechanistic Investigations.

SummaryMononuclear metal-peroxo species are invoked as the key intermediates in metalloenzymatic or synthetic catalysis. However, either transience or sluggishness reactivity of synthetic analogs of metal-peroxo species impedes our understanding of oxygen activation mechanism. Herein, we designed and characterized a dioxygen-derived mononuclear osmium-peroxo complex, in which the peroxo ligand is stabilized by internally aromatic metallacycle. We demonstrate that the osmium-peroxo species shows catalytic activity toward promoterless alcohol dehydrogenations. Furthermore, computational studies provide a new mechanism for the osmium-peroxo-mediated alcohol oxidation, starting with the concerted double-hydrogen transfer and followed by the generation of osmium-oxo species. Interestingly, the internally aromatic metallacycle also plays a vital role in catalysis, which mediates the hydrogen transfer from osmium center to the distal oxygen atom of Os–OOH moiety, thus facilitating the Os–OOH→Os=O conversion. We expect that these insights will advance the development of aromatic metallacycle toward aerobic oxidation catalysis.

Efficient Quantum Mechanical Calculations of Mode-Specific Tunneling Splittings upon Fundamental Excitation in the Dimer of Formic Acid.

The formic acid dimer (FAD) is an important benchmark system for understanding the double hydrogen transfer process. Most recently, Zhang et al. measured a few tunneling splittings upon fundamental excitation of FAD precisely (Zhang, Y. et al. J. Chem. Phys. 2017, 146, 244306); however, relevant theoretical studies are very limited. Here, we present a multidimensional quantum dynamics study on mode-specific tunneling splittings upon fundamental excitation in FAD with an efficient theoretical scheme developed by our group in which the process-oriented basis function customization strategy is combined with the preconditioned inexact spectral transform method. Various mode-specific tunneling splittings upon fundamental excitation are systematically calculated, and interesting mode-specific excitation effects on tunneling rate are identified. In particular, the calculated tunneling splittings for the ν22 and ν21 states are in good agreement with experiment, and the remarkable mode-specific suppression effects upon excitation should result from that the antisymmetric vibrational modes hinder the concerted double H-transfer. The present work is helpful to acquire a better understanding of the mode-specific excitation effects on tunneling processes.

Theoretical insight into the solvent effect on the stoichiometric reduction of carbonyl compounds by ammonia borane and N‐methyl amine borane

AbstractFor the traditional reduction of ketones and aldehydes, NH3BH3 (AB) and N‐methyl amine borane (M nAB) have been effective reducing agents. However, the reaction process is indefinite and different mechanisms have been proposed; also the solvent effect, which is closely related to the mechanism, has not been considered seriously. Here we employ density functional theory to carry out a comprehensive study on the mechanism. The calculated free energy of the concerted double hydrogen transfer process is lower than the hydroboration mechanism by 4.7 kcal/mol, which indicates that reduction of carbonyl by AB is likely due to be the concerted double hydrogen transfer in both aprotic (tetrahydrofuran) and protic (MeOH) solvents. For the reduction by M nAB, the corresponding free energies of all reactions are higher than those of AB. Meanwhile, the reduction of benzaldehyde by M nAB (n = 1, 2) also favors a concerted double hydrogen transfer rather than hydroboration.

Influence of local microenvironment on the double hydrogen transfer in porphycene.

We performed time-resolved transient absorption and fluorescence anisotropy measurements in order to study tautomerization of porphycene in rigid polymer matrices at cryogenic temperatures. Studies were carried out in poly(methyl methacrylate) (PMMA), poly(vinyl butyral) (PVB), and poly(vinyl alcohol) (PVA). The results prove that in all studied media hydrogen tunnelling plays a significant role in the double hydrogen transfer which becomes very sensitive to properties of the environment below approx. 150 K. We also demonstrate that there exist two populations of porphycene molecules in rigid media: "hydrogen-transferring" molecules, in which tautomerization occurs on time scales below 1 ns and "frozen" molecules in which double hydrogen transfer is too slow to be monitored with nanosecond techniques. The number of "frozen" molecules increases when the sample is cooled. We explain this effect by interactions of guest molecules with a rigid host matrix which disturbs symmetry of porphycene and hinders tunnelling. Temperature dependence of the number of hydrogen-transferring molecules suggests that the factor which restores the symmetry of the double-minimum potential well in porphycene are intermolecular vibrations localized in separated regions of the amorphous polymer.

Chiral phosphoric acid catalyzed asymmetric transfer hydrogenation of bulky aryl ketones with ammonia borane

An asymmetric transfer hydrogenation of bulky aryl ketones with ammonia borane was successfully realized with chiral phosphoric acid (CPA) as catalyst and water as additive. A variety of optically active secondary alcohols were obtained in good to high yields with up to 77% ee. The reaction likely proceeded through a Brønsted acid-promoted double-hydrogen transfer between ketones and ammonia borane via a six-membered concerted transition state.

Electron-induced ionization of undeuterated and deuterated benzoic acid isopropyl esters and nicotinic acid isopropyl esters: Some implications for the mechanism of the McLafferty rearrangement.

Electron ionization mass spectra, ionization, and appearance energies and bond energies (as dissociation energies) are reported for benzoic acid-1-methyl-ethyl ester (BAIPE), benzoic acid-1-deutero-1-methyl-ethyl ester (BAIPED1), benzoic acid-2,2,2-trideutero-1-trideuteromethyl-ethyl ester (BAIPED6) as well as nicotinic acid-1-methyl-ethyl ester (NAIPE), nicotinic acid-1-deutero-1-methyl-ethyl ester (NAIPED1), and nicotinic acid-2,2,2-trideutero-1-trideuteromethyl-ethyl ester (NAIPED6). Ionization energies of 9.39 eV for BAIPE, 9.40 eV for BAIPED1, 9.26 eV for BAIPED6 as well as 9.70 eV for NAIPE, 9.79 eV for NAIPED1, and 9.65 eV for NAIPED6 were determined. A gas-phase formation enthalpy of = (-4.10 ± 0.1) eV for BAIPE is calculated as well as = (-3.35 ± 0.1) eV for NAIPE. Molecular ions show two main fragmentation pathways. The first is a classical McLafferty rearrangement, characterized by the transfer of one γ-hydrogen atom from the isopropyl ester chain leading to the ions of the corresponding acid and neutral propene. The second is the double hydrogen transfer from the ester chain leading to the formation of the protonated acid and a C3H5√ allyl radical. For BAIPE, both hydrogen atoms originate from the methyl groups of the aliphatic chain with a probability of ≥98%, whereas the C-1-hydrogen is transferred with a probability of ≤2%. For NAIPE, both hydrogen atoms originate from the methyl groups of the aliphatic chain with a probability of 90%. Experimental proton affinities of PA = (8.75 ± 0.2) eV for benzoic acid and PA = (8.43 ± 0.2) eV for nicotinic acid are derived. For the protonation of the carbonyl group, B3LYP DFT calculations yielded PA = 8.66 eV for benzoic acid and PA = 8.41 eV for nicotinic acid. The overall fragmentation mechanism is explained with the initial formation of a 1,5-distonic ion by transfer of the first hydrogen. For the transfer of the second hydrogen, an intermediate ion/neutral complex is formulated.

Elucidating the Nuclear Quantum Dynamics of Intramolecular Double Hydrogen Transfer in Porphycene.

We address the double hydrogen transfer (DHT) dynamics of the porphycene molecule, a complex paradigmatic system in which the making and breaking of H-bonds in a highly anharmonic potential energy surface require a quantum mechanical treatment not only of the electrons but also of the nuclei. We combine density functional theory calculations, employing hybrid functionals and van der Waals corrections, with recently proposed and optimized path-integral ring-polymer methods for the approximation of quantum vibrational spectra and reaction rates. Our full-dimensional ring-polymer instanton simulations show that below 100 K the concerted DHT tunneling pathway dominates but between 100 and 300 K there is a competition between concerted and stepwise pathways when nuclear quantum effects are included. We obtain ground-state reaction rates of 2.19 × 1011 s–1 at 150 K and 0.63 × 1011 s–1 at 100 K, in good agreement with experiment. We also reproduce the puzzling N–H stretching band of porphycene with very good accuracy from thermostated ring-polymer molecular dynamics simulations. The position and line shape of this peak, centered at around 2600 cm–1 and spanning 750 cm–1, stem from a combination of very strong H-bonds, the coupling to low-frequency modes, and the access to cis-like isomeric conformations, which cannot be appropriately captured with classical-nuclei dynamics. These results verify the appropriateness of our general theoretical approach and provide a framework for a deeper physical understanding of hydrogen transfer dynamics in complex systems.

Nature of Large Temporal Fluctuations of Hydrogen Transfer Rates in Single Molecules.

Double hydrogen transfer was monitored in single molecules of parent porphycene and its tetra- t-butyl derivative using confocal fluorescence microscopy. The molecules have been embedded in a polymer matrix. Under such conditions, a significant fraction of the population reveals a huge decrease of the tautomerization rate with respect to the value obtained from ensemble studies in solution. This effect is explained by a model that assumes that the rate is determined by the reorganization coordinate that involves slow relaxation of the polymer matrix. The model provides indirect evidence for the dominant role of tunneling. It is proposed that tautomerization in single molecules of the porphycene family can be used to probe polymer relaxation dynamics on the time scale ranging from picoseconds to minutes.

Unusual effects in single molecule tautomerization: hemiporphycene.

Parent hemiporphycene, a recently obtained constitutional isomer of porphyrin, exists in room temperature solutions and polymer matrices in the form of two trans tautomers interconverting via double hydrogen transfer. Using confocal fluorescence microscopy, it was possible to monitor tautomerization in single hemiporphycene molecules embedded in a PMMA film by monitoring the spectral and temporal evolution of their fluorescence spectra. The emission spectra of the two tautomeric forms are similar to those obtained from ensemble studies. However, the analysis of temporal spectral evolution reveals effects not detected in the bulk. For some single molecules, a large decrease of tautomerization rate was observed. This is interpreted as an indication of multidimensional character of the tautomerization coordinate and coupling of the reaction with the polymer relaxation processes. In addition, fluorescence lifetimes obtained for single molecules are significantly shorter than those measured for the bulk. It is proposed that the shortening is caused by environment-induced distortion of the molecule, which enhances the S0← S1 internal conversion rate by lowering the barrier to excited state single hydrogen transfer. This effect seems to reflect the specific morphology of thin (30 nm) polymer samples, because it is not observed in ensemble studies carried out using thick (tens of micrometers or more) PMMA films.