Solvent Effects on Internal Rotational Barriers in Furfural. NMR Measurements and ab-Initio Molecular Orbital Methods Using Continuum Models Alex D. Bain* and Paul Hazendonk Department of Chemistry, McMaster UniVersity, Hamilton, Ontario, Canada L8S 4M1 ReceiVed: May 6, 1997; In Final Form: June 30, 1997 X Modern experimental and theoretical methods for determining solvent effects on internal rotational barriers in small molecules are compared. The barrier to rotation of the aldehyde group in furfural dissolved in toluene, acetone, and methanol is used as a test case. Ab-initio molecular orbital methods such as self consistent reaction field (SCRF) calculations, performed with the Onsager and isodensity surface polarized continuum (IPC) model, predict an increase in barrier with increasing solvent dielectric constant, ǫ. A combination of three nuclear magnetic resonance experiments are used to obtain rate data over 6 orders of magnitude representing an approximately 150 K temperature range. Activation parameters were obtained with errors less than 1 kJ/mol and 6 J/(mol K) for ΔH q and ΔS q , respectively. In acetone and toluene large ΔS q values of -26 and 20 J/(mol K) were found, along with a ΔS° of 10 J/(mol K) in both solvents. In methanol no appreciable values for ΔS q and ΔS° were measured. The ΔH q for toluene, acetone, and methanol are 48.6, 40.2, and 46.4 kJ/mol, respectively, which do not obey a simple relationship with ǫ. This indicates that the solvent effect is likely more complex than just the effect of a solvent reaction field. The large ΔS q values support this and also imply that equating ΔG q and ΔH q is not always justified, even for aprotic solvents. The behavior of these three barriers and their corresponding ΔS q are discussed in terms of direct solvent-solute interactions. Introduction Rotations of chemical bonds in molecules are seldom “free”. In other words there is always some barrier to rotation, which can furthermore depend on solvent. Studies into solvent effects on these processes are primarily concerned with measurement or theoretical predictions. Measurements are achieved mainly by nuclear magnetic resonance (NMR), microwave, and infrared (IR) spectroscopies. Barriers are computed using molecular orbital calculations of the solute in the presence of the reaction field due to the solvent. The main aim of this study is to compare the most recent methods of measurement with predic- tion, on a sample system. Usually NMR rate measurements are made with line shape fitting procedures. 1-9 Due to limits on the temperature range over which rate measurements can be made, barriers are often reported as ΔG q . 8,10-14 To compare these barriers with calcula- tions (which give ΔH q ), ΔS q is often assumed to be zero. 8,15 This assumption is not unreasonable since these are unimolecular processes. However, there are cases where ΔS q is observed to be significantly nonzero. 16,17 Calculations of internal rotational barriers in solvent usually include continuum models, 18-21 which compute the electrostatic contribution to the free energy of solvation. The total energy is just a combination of the free energy of solvation with the gas phase energy. To make the model more complete, the electrostatic solvation energy is often accompanied by contribu- tions from cavitation and dispersion energies. 20,22 Recently, the electrostatic interaction has been incorporated into the Fock operator of the solute, including it in the self-consistent cycles which optimize the electron density. This allows the solute to be polarized by the solvent field. 23-25 Second derivatives of this self consistent reaction field energy, with respect to the nuclear coordinates, are now readily determined, making transition state searches and frequency calculations possible. 26,27 With these developments, barriers in liquid phase are as readily obtained as in gas phase, with some additional computational effort. It should be stressed however that these methodologies do not account for direct solute-solvent interactions. In order to obtain good experimental values of ΔH q and ΔS q , rate measurements are needed over as wide a range as possible. Recently this laboratory developed a technique that employs three complementary NMR experiments. 5,7,28-32 These, when combined, are capable of generating rate data over 6 orders of magnitude, corresponding to temperature ranges of ca. 150 °C. Measurements made on furfural in acetone revealed that the ΔH q was much smaller than previously seen in polar solvents and a large negative ΔS q was observed. 29 ΔG q (298) was in line with the previous experimental and theoretical studies. Consequently ignoring the entropy of activation is not always justified and equating ΔG q with ΔH q can be misleading. This study will compare barriers calculated by recently developed computational methodologies with those measured by the most accurate NMR methods for furfural in toluene, acetone, and methanol. Measurements will be carried out with the three NMR experiment techniques, and computations will employ self consistent reaction field (SCRF) methods using the Onsager 23-25 and Tomasi’s isodensity surface polarized con- tinuum (IPC) models. 33,34 The importance of considering ΔS q will be discussed. Methodology Rate Measurements. The most common way of measuring rates by NMR is with line shape methods. These rates are only accurate when the line shape in question is broad, 8,28,29 which occurs when the line width is dominated by the contribution from exchange and other line-broadening factors are small in comparison. In the extreme ranges of measurement, both when the rates are slow and fast, the lines are narrow and other line- broadening factors become significant. 35 As a result the rates * Author to whom correspondence should be addressed. X Abstract published in AdVance ACS Abstracts, August 15, 1997. 7182 J. Phys. Chem. A 1997, 101, 7182-7188 S1089-5639(97)01520-X CCC: $14.00 © 1997 American Chemical Society