Influence of inter- and intramolecular hydrogen bonding on kemp decarboxylations from QM/MM simulations

The Kemp decarboxylation reaction for benzisoxazole-3-carboxylic acid derivatives has been investigated using QM/MM calculations in protic and dipolar aprotic solvents. Aprotic solvents have been shown to accelerate the rates of reaction by 7-8 orders of magnitude over water; however, the inclusion of an internal hydrogen bond effectively inhibits the reaction with near solvent independence. The effects of solvation and intramolecular hydrogen bonding on the reactants, transition structures, and the rate of reaction are elucidated using two-dimensional potentials of mean force (PMF) derived from free energy perturbation calculations in Monte Carlo simulations (MC/FEP). Free energies of activation in six solvents have been computed to be in close agreement with experiment. Solute-solvent interaction energies show that poorer solvation of the reactant anion in the dipolar aprotic solvents is primarily responsible for the observed rate enhancements over protic media. In addition, a discrepancy for the experimental rate in chloroform has been studied in detail with the conclusion that ion-pairing between the reactant anion and tetramethylguanidinium counterion is responsible for the anomalously slow reaction rate. The overall quantitative success of the computations supports the present QM/MM/MC approach, which features PDDG/PM3 as the QM method.     

The conformational composition of 3-buten-1-ol, the importance of intramolecular hydrogen bonding

The conformations of 3-buten-1-ol (1), and its model compounds cis-6-methyl-3-cyclohexen-1-ol (6), 3-cyclopenten-1-ol (7) and epicholesterol (9) have been investigated by FT-IR and ¹H NMR spectroscopy. The energies and geometries of 1, 6 and 7 were also investigated by molecular mechanics, semiempirical molecular orbital and ab initio calculations, while 9 was investigated by molecular mechanics only. The objective of the work was to study the conformational composition and importance of intramolecular OH…π hydrogen bonding for this composition in 1. Only two conformers of 1 have a geometrical possibility for intramolecular hydrogen bonding: Conformers 12 and 13 (Fig. 1). Compounds 6 and 7 were used as models for Conformer 12, while 9 was used as a model for Conformer 13. The investigations showed that Conformer 13 is the only hydrogen-bonded conformer, and that Conformer 12 is not intramolecularly hydrogen bonded. Conformer 13 was the most populated conformer, while Conformer 12 was hardly populated. The combination of experimental and theoretical data, and the use of model compounds was found necessary to obtain this conclusion.     

Solvent and substituent effects on the conformational equilibria and intramolecular hydrogen bonding of 4-substituted-2-hydroxybenzaldehydes

By applying the B3LYP/6-31G(d) method with the SCIPCM model on seven 4X substituted 2-hydroxybenzaldehydes, some structural characteristics related with their conformational equilibria and intramolecular hydrogen bonds have been clarified. The compounds are almost completely under the planar conformation characterized by a strong intramolecular hydrogen bond, which decreases in those solvents that possess a higher hydrogen bond donating capability and polarity. The substituents exert a marked influence on the conformational equilibrium constants and the strength of the IHB. Moreover, the excellent Hammett-type equations obtained support the proposed conformational reactions to quantify the IHB in the o-hydroxybenzaldehydes studied.     

A microwave and quantum chemical study of the conformational properties and intramolecular hydrogen bonding of 1-fluorocyclopropanecarboxylic acid

The structural and conformational properties of 1-fluorocyclopropanecarboxylic acid have been explored by microwave spectroscopy and a series of ab initio (MP2/6-311++G(d,p) level), density functional theory (B3LYP/aug-cc-pVTZ level), and G3 quantum chemical calculations. Four "stable" conformers, denoted conformers I-IV, were found in the quantum chemical calculations, three of which (conformers I -III) were predicted to be low-energy forms. Conformer I was in all the quantum chemical calculations predicted to have the lowest energy, conformer III to have the second lowest energy, and conformer II to have the third lowest energy. Conformers II and III were calculated to have relatively large dipole moments, while conformer I was predicted to have a small dipole moment. The microwave spectrum was investigated in the 18-62 GHz spectral range. The microwave spectra of conformers II and III were assigned. Conformer I was not assigned presumably because its dipole moment is comparatively small. Conformer II is stabilized by an intramolecular hydrogen bond formed between the fluorine atom and the hydrogen atom of the carboxylic acid group. Conformer III has a synperiplanar orientation for the F-C-C=O and H-O-C=O chains of atoms. Its dipole moment is: mua = 3.4(10), mub = 10.1(13), and muc = 0.0 (assumed) and mu(tot) = 10.6(14) x 10(-30) C m [3.2(4) D]. Several vibrationally excited states of the lowest torsional mode of each of II and III were also assigned. The hydrogen-bonded conformer II was found to be 2.7(2) kJ/mol less stable than III by relative intensity measurements. Absolute intensity measurements were used to show that the unassigned conformer I is the most abundant form present at a concentration of roughly 65% at room temperature. Conformer I was estimated to be ca. 5.0 kJ/mol more stable than the hydrogen-bonded rotamer (conformer II) and ca. 2.3 kJ/mol more stable than conformer III. The best agreement with the theoretical calculations is found in the MP2 calculations, which predict conformer I to be 5.1 kJ/mol more stable than III and 1.7 kJ/mol more stable than II.     

An NMR investigation of the importance of intramolecular hydrogen bonding in determining the conformational equilibrium of ethylene glycol in solution

Although conformational analysis by NMR of ethylene glycol indicates generally strong preferences for the gauche conformation in solvents ranging from water to chloroform, the bulk of the NMR evidence indicates that intramolecular hydrogen bonding between the hydroxyl groups is unlikely to be a significant factor in determining that preference, except possibly in fairly non-polar solvents. The 'gauche effect' is clearly very important, especially in aqueous solution.     

Vapor pressure and intramolecular hydrogen bonding in fluorotelomer alcohols

Vapor pressure and aqueous solubility are important parameters used to estimate the potential for transport of chemical substances in the atmosphere. For fluorotelomer alcohols (FTOHs), currently under scrutiny by environmental scientists as potential precursors of persistent perfluorocarboxylates (PFCAs), vapor pressure is the more significant property since these compounds are only very sparingly soluble in water. We have measured the vapor pressures of a homologous series of fluorotelomer alcohols, F(CF2CF2)nCH2CH2OH (n = 2-5), in the temperature range 21-250 degrees C by three independent methods: (a) a method suitable for very low vapor pressures at ambient temperatures (gas-saturation method), (b) an improved boiling point method at controlled pressures (Scott method), and (c) a novel method, requiring milligram quantities of substance, based on gas-phase NMR, a technique largely unfamiliar to chemists and holding promise for studies of relevance to environmental chemistry. The concordant values obtained indicate that recently published vapor pressure data overestimate the vapor pressure at ambient temperature, and therefore the volatility, of this series of fluorinated compounds. It was suggested that substantial intramolecular -O-H...F- hydrogen bonding between the hydroxylic proton and the two fluorines next to the ethanol moiety was responsible for their putative high volatility. Therefore, we have used gas-phase NMR, gas-phase FTIR, 2D NMR heteronuclear Overhauser effect measurements, and high-level ab initio computations to investigate the intramolecular hydrogen bonding in fluorotelomer alcohols. Our studies unequivocally show that hydrogen bonding of this type is not significant and cannot contribute to and cause unusual volatility. The substantially lower vapor pressure at ambient temperatures than previously reported resulting from our work is important in developing a valid understanding of the environmental transport behavior of this class of compounds.     

Studies of intramolecular hydrogen bonding in protonated and non-protonated hexahydropyridinobenzodioxins

The conformational stability of hexahydropyridobenzodioxin and related derivatives in both protonated and non-protonated forms have been investigated by means of ab initio molecular orbital methods as well as semi-empirical AM1 and PM3 methods. One of the cis conformers (cis2e) has been found to be most stable due to the formation of an intramolecular hydrogen bond, other conformers including the trans isomer cannot form this interaction but are of different stability because of the orientation of the polar oxygens and the nitrogen. The effect of the intramolecular hydrogen bonding on the stability of hexahydropyridobenzodioxin and its methylated derivatives has been examined using various basis sets levels. In protonated form, both the semi-empirical and ab initio calculations give excellent agreement in energetic order; however, different orderings of conformer stabilities are observed by different computational methods in non-protonated form. The results provide insight into the intramolecular hydrogen bonding in computational studies of biologically important molecules.     

Preorganization-enhanced halogen bonding via intramolecular hydrogen bonding: a theoretical study

Structural Chemistry - Cationic and neutral halogen bonding (XB) donors use two types (I and II) of intramolecular hydrogen bonding (HB) to preorganize structures and increase the efficiency of...     

Stereochemistry of cytidine: conformational analysis and hydrogen bonding

The energy calculations using the INDO molecular orbital method and classical potential function show that the syn conformation of pyrimidine nucleosides having the C_(2')-endo or C_(2')-endo-C_(3')-endo sugar ring puckering is as stable as the corresponding anti form.The O_(2')-O_(2') base-ribose hydrogen bonding significantly alters the Φ_CN conformation by confining the allowed Φ_CN ranges to about 150–210°.     

Intramolecular interactions and intramolecular hydrogen bonding in conformers of gaseous glycine

Ab initio calculations at the MP2/6‐311++G** level of theory led recently to the identification of 13 stable conformers of gaseous glycine with relative energies within 11 kcal/mol. The stability of every structure depends on subtle intramolecular effects arising from conformational changes. These intramolecular interactions are examined with the tools provided by the Atoms In Molecules (AIM) theory, which allows obtaining a wealth of quantum mechanics information from the molecular electron density ρ( r ). The analysis of the topological features of ρ( r ) on one side and the atomic properties integrated in the basins defined by the gradient vector field of the density on the other side makes possible to explore the different intramolecular effects in every conformer. The existence of intramolecular hydrogen bonds on some conformers is demonstrated, while the presence of other stabilizing interactions arising from favorable conformations is shown to explain the stability of other structures in the potential energy surface of glycine. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 702–716, 2001     

Tunnel effects on inter- and intramolecular hydrogen transfer reactions of transient dihydro- and hexahydrocarbazoles

We examine inter- and intramolecular hydrogen-transfer processes in two related metastable dihydrocarbazoles in nonpolar solvents of different viscosity and compare them with similar transfer processes in transient hexahydrocarbazoles. N-ethyldiphenylamine (A′) and N-ethyl-2,6-dimethyldiphenylamine (A) photocyclize in their triplet states, yielding the triplet states of the zwitterionic dihydrocarbazoles ³Z′* and ³Z*, respectively, which subsequently relax to their metastable singlet ground states ¹Z′ and ¹Z′. In spite of their similarity, the two transients ¹Z′ and ¹Z stabilize by completely different pathways: the unsubstituted transient ¹Z′ is converted into N-ethylcarbazole (C) and an N-ethyltetrahydrocarbazole (THC) by a bimolecular disproportionation reaction. The methylsubstituted intermediate ¹Z is converted into a stable dihydrocarbazole (D) by a sigmatropic, intramolecular [1,8]-H-shift and by an intermolecular, mutual hydrogen-exchange reaction within the encounter complex ¹(ZZ) which yields two molecules of D. The rates of the intra- and of the intermolecular transfer reaction of ¹Z are governed by tunnel effects. The rate of the intramolecular tunnel process does not depend on solvent friction and becomes temperature independent at low temperatures. The rate of the intermolecular, reaction-controlled exchange reaction ¹(ZZ) → 2 ¹D becomes also temperature independent if the solvent is fluid enough. In more viscous solvents the reaction becomes diffusion controlled and, therefore, strongly temperature dependent. The intermolecular disproportionation reaction 2 ¹Z′ → C + THC is also reaction controlled but no tunnel effects are observed.     

Spectroscopic and computational studies of the intramolecular hydrogen bonding of 2-indanol

2-Indanol in its most stable form is stabilized by internal hydrogen bonding, which exists between the hydroxyl hydrogen atom and the pi-cloud of the benzene ring. A comprehensive ab initio calculation using the MP2/cc-pVTZ level of theory showed that 2-indanol can exist in four possible conformations, which can interchange through the ring-puckering vibration and the internal rotation of the OH group on the five-membered ring. A potential energy surface in terms of these two vibrational coordinates was calculated. Density functional theory calculations were used to predict the vibrational frequencies and to help in normal mode assignments. Fluorescence excitation spectra of 2-indanol confirm the presence of the four conformers in the electronic ground and excited states. The spectral intensities indicate that, at 90 degrees C, 82% of the molecules exist in its most stable form with the intramolecular hydrogen bonding. The other isomers are present at approximately 11, 5, and 3%. The MP2/6-311++G(d,p) calculation predicts a distribution of 70, 13, 9, and 8% at 90 degrees C, the experimental sample temperature.     

On the extent of intramolecular hydrogen bonding in gas-phase and hydrated 1,2-ethanediol

We investigate the quantum dynamical nature of hydrogen bonding in 1,2-ethanediol and monohydrated 1,2-ethanediol using different levels of ab initio theory. Global full-dimensional potential energy surfaces were constructed from PW91/cc-pVDZ, B3LYP/cc-pVDZ, and MP2/cc-pVDZ ab initio data for gas-phase and monohydrated 1,2-ethanediol, using a modified Shepard interpolation scheme. Zero-point energies and nuclear vibrational wave functions were calculated on these surfaces using the quantum diffusion Monte Carlo algorithm. The nature of intra- and intermolecular hydrogen bonding in these molecules was investigated by considering a ground-state nuclear vibrational wavefunction with reduced complete nuclear permutation and inversion (CNPI) symmetry. Separate wavefunction histograms were determined from the ground-state nuclear vibrational wavefunction by projection into bondlength coordinates. The O-H and O-O wavefunction histograms and vibrationally averaged distances were then used to probe the extent of intra- and intermolecular hydrogen bonding. From these data, we conclude that gas-phase ethanediol may possess a weak hydrogen bond, with a relatively short O-O distance but no detectable proton delocalization. Monohydrated ethanediol was found to exhibit no intramolecular hydrogen bonding but instead possessed two intermolecular hydrogen bonds, indicated by both shortening of the O-O distance and significant proton delocalization. The degree of proton delocalization and shortening of the vibrationally averaged O-O distance was found to be dependent on the ab initio method used to generate the potential energy surface (PES) data set.     

Density functional theory and atoms-in-molecules investigation of intramolecular hydrogen bonding in derivatives of malonaldehyde and implications for resonance-assisted hydrogen bonding

A density functional theory (DFT) and atoms-in-molecules (AIM) analysis has been applied to the intramolecular hydrogen bonding in the enol conformers of malonaldehyde and its fluoro-, chloro-, cyano-, and nitro-substituted derivatives. With the B3LYP/6-311++G(2d,p) method, good agreement between the DFT geometries and published experimental structures has been found. The donor-acceptor distance was also varied in a series of constrained optimizations in order to determine if energetic, structural, and topological trends associated with intermolecular hydrogen bonding remain valid in the intramolecular case. At very short donor-acceptor distances (<2.24 A), the hydrogen is symmetrically located between donor and acceptor; at distances longer than this, the hydrogen bonding is no longer symmetric. The AIM methodology has been applied to explore the topology of the electron density in the intramolecular hydrogen bonds of the chosen model systems. Most AIM properties for intramolecular hydrogen bond distances longer than 2.24 A show smooth trends, consistent with intermolecular hydrogen bonds. Integrated AIM properties have also been used to explore the phenomenon of resonance-assisted hydrogen bonding (RAHB). It is shown that as the donor-acceptor distance is varied, pi-electron density is redistributed among the carbon atoms in the intramolecular hydrogen bond ring; however, contrary to prior studies, the integrated atomic charges on the donor-acceptor atoms were found to be insensitive to variation of hydrogen-bonding distance.     

Interplay between intramolecular resonance-assisted hydrogen bonding and aromaticity in o-hydroxyaryl aldehydes

In this work, we analyze a series of o-hydroxyaryl aldehydes to discuss the interrelation between the resonance-assisted hydrogen bond (RAHB) formation and the aromaticity of the adjacent aromatic rings. As compared to the nonaromatic reference species (malonaldehyde), the studied compounds can be separated into two groups: first, the set of systems that have a stronger RAHB than that of the reference species, for which there is a Kekulé structure with a localized double CC bond linking substituted carbon atoms; and second, the systems having a weaker RAHB than that of the reference species, for which only pi-electrons coming from a localized Clar pi-sextet can be involved in the RAHB. As to aromaticity, there is a clear reduction of aromaticity in the substituted ipso ring for the former group of systems due to the formation of the RAHB, while for the latter group of species only a slight change of local aromaticity is observed in the substituted ipso ring.