Kinetic and equilibrium lithium acidities of substituted toluenes: semitheoretical Brönsted correlations.

Semitheoretical Brönsted correlations are compared between previously measured experimental rates of hydrogen isotope exchange of substituted toluenes labeled in the α-position and relative equilibrium acidities computed at several theory levels. The Brönsted correlations show less scatter at the Hartree-Fock level than at higher theory levels. This effect is rationalized on the basis of enhanced steric effects in the more constrained structures of the higher theory levels.

Ion pair pKs of some amines: extension of the computed lithium pK scale.

The pK of p-(methylamino)biphenyl, 1, on our Li scale, pK(Li) = 22.09, compared to the cesium scale, pK(Cs) = 28.60. For hexamethyldisilazane, HMDS, pK(Li) = 23.05, pK(Cs) = 29.26. These results are those for the monomers in THF; corrections were made for dimers present in some cases. The pK(Li) of these two amines fit well the previously found correlation with Hartree-Fock calculations at 6-31+g(d) using RLi coordinated with three dimethyl ethers as a computational model for RLi in THF. The results are also compared with earlier pK(Li)s reported from equilibria with lithium amides in which aggregation was not considered.

AIM and NPA studies of the role of polarization in electronic structures.

Atomic charges, as measured by Atoms in Molecule (AIM) or Natural Population Analyses (NPA), of the enolate anions of acetaldehyde and crotonaldehyde and of pentadienyl anion and cation show both charge transfer and polarization effects. In general, normal resonance structures and "curved arrow" symbolism give good representations of π-electron distributions, but back-polarizations in the σ-system complicate these electronic structures and can obscure the correspondence to resonance symbols. Twisting a vinyl group to orthogonality disrupts the π-system, but the vinyl group retains significant charge transfers and polarizations. The role of polarization is also demonstrated by the effect of external positive and negative charges on the electronic structure of ethylene. The π-electronic changes again are straightforward but are changed significantly by σ-polarizations. The polarizability of ethane is about half that of ethylene.

Ab initio modeling of organolithium equilibria.

Experimental ion pair pK's of monomeric contact ion pair lithium salts in THF from our previous studies give good correlations with ab initio calculations at the Hartree-Fock 6-31+g(d) level. PCM methods were found to be inadequate in nonpolar organic solvents, and dielectric solvation was not used in the correlations. Specific coordination of two or three ether solvent molecules with lithium was found to be satisfactory. These correlations include carboxamides, amines, dithianes, sulfones, and sulfoxides, as well as some ketones, beta-diketones, and the lithium salts of dianions.

Kinetic and equilibrium lithium acidities of arenes: theory and experiment.

Kinetic acidities of arenes, ArH, measured some time ago by hydrogen isotope exchange kinetics with lithium cyclohexylamide (LiCHA) in cyclohexylamine (CHA) show a wide range of reactivities that involve several electronic mechanisms. These experimental reactivities give an excellent Brønsted correlation with equilibrium lithium ion pair acidities (pK(Li)) derived as shown recently from computations of ArLi.2E (E = dimethyl ether). The various electronic mechanisms are well modeled by ab initio HF calculations with modest basis sets. Additional calculations using NH(3) as a model for CHA further characterize the TS of the exchange reactions. The slopes of Brønsted correlations of ion pair systems can vary depending on the nature of the ion pairs.

Perspectives on computational organic chemistry.

The author reviews how his early love for theoretical organic chemistry led to experimental research and the extended search for quantitative correlations between experiment and quantum calculations. The experimental work led to ion pair acidities of alkali-organic compounds and most recently to equilibria and reactions of lithium and cesium enolates in THF. This chemistry is now being modeled by ab initio calculations. An important consideration is the treatment of solvation in which coordination of the alkali cation with the ether solvent plays a major role.

Theoretical study of the effect of coordinating solvent on ion pair SN2 reactions: the role of unsymmetrical transition structures.

Computations are reported at the HF/6-31+g* level for ion pair SN2 reactions of methyl, ethyl, n-propyl, isopropyl, and allyl halides with LiX.E, LiX.2E, and LiX.3E (X = F, Cl, Br; E = dimethyl ether as a model for THF). Some calculations were also done at the MP2, B3LYP, and mPW1PW91 levels. In addition to normal SN2-type (type I) transition structures (TSs), novel unsymmetrical TSs were found in which the Li is coordinated to a single halide. With LiX.2E, such structures are already competitive with the type I structures, and with LiX.3E, only the type II structures were found. With incorporation of dielectric solvation, the type II structures are relatively even more stable. The results suggest that such structures are better models for ion pair displacement reactions in ethereal solvents.

Evaluation of Two Computational Models Based on Different Effective Core Potentials for Use in Organocesium Chemistry.

The performance of two computational models was evaluated in describing some aggregated structures, the bond lengths and dimerization energies of cesium halides, aquation energies of the cesium cation, and protonation energies of a range of organocesium compounds. One model used the Hay-Wadt (HW) effective core potential (ECP) and a double-ζ valence basis set on Cs; the other used the Ross ECP with two polarization functions on Cs. In both models, the standard 6-31+G** basis was used for the other atoms. At the Hartree-Fock (HF) level, the Ross ECP was found to give geometries and energies in good agreement with experimental results. Second-order Møller-Plesset calculations with this model gave only modestly improved results compared to HF; the B3LYP level gave variable results with unsatisfactory energies. Although the HW model is generally less satisfactory, it often shows comparable trends to those of the Ross model.

Ion pair aggregates and reactions; experiment and theory.

Two methods have been developed for determining the aggregation equilibrium constants of lithium enolates based on the change in UV-vis spectrum with concentration and the effect of aggregation on proton-transfer equilibria. Dimers and tetramers are common. Substitution alpha to the carbonyl group generally reduces aggregation. Kinetic studies show that S(N)2 alkylations generally occur with the monomers, even in the presence of large amounts of aggregate. The qualitative chemistry is well modeled by ab initio computations at the HF level with modest basis sets; in these studies solvation is modeled by a combination of coordination of lithium cation with an ether oxygen and the electrostatic interaction of the resulting dipoles and quadrupoles with the solvent dielectric continuum.

Kinetic acidity of aliphatic hydrocarbons. Hydrogen isotope exchange with cesium cyclohexylamide in cyclohexylamine.

Kinetic acidities are reported for methane, ethane, propane, cyclopropane, isobutane, neopentane, tetramethylbutane, norbornane, nortricyclene, and adamantane by tritiodeprotonation or deuteriodeprotonation in cyclohexylamine catalyzed by cesium cyclohexylamide.

Basicity of some phosphines in THF.

[reaction: see text] The reaction of several phosphines with an acidic indicator gives both ion pairs and free ions. The value obtained for the pKa of tribenzylphosphine is shown to be reasonable by MO computations. An important limitation is demonstrated for the Fuoss equation of dissociation of ion pairs.

A computational study of the effect of bending on secondary kinetic isotope effects in SN2 transition states.

Using conventional transition state theory, the secondary deuterium kinetic isotope effect (KIE) in the inversion SN2 reaction of CH3F and F- is calculated to be small, 0.98 (T = 298 K). This is shown to be the result of a balance among opposing entropy and enthalpy terms. By contrast, KIE in the retention SN2 mechanism is calculated to be large (1.5). Accordingly, KIE is a potential observable for discriminating between the two mechanisms. Large KIE's are also found for the inversion and retention mechanisms of the ion pair reactions between CH3F and LiF. All of the transition structures leading to large KIE's have a bent FCF angle and an imaginary frequency that is sensitive to deuterium labeling.

Ion pair first and second acidities of some beta-diketones and aggregation of their lithium and cesium enediolates in THF.

Ion pair pK values were measured for three beta-diketones in THF, 1-3, with lithium and cesium counterions. The results showed variations with concentration indicative of aggregation of the metal enolates to dimers. Similarly, ion pair pK values could be determined for some of these metal enolates going to the corresponding dimetal dienediolates which were also found to form dimers. These equilibria are more complicated to analyze because aggregation affects both sides of the proton transfer equilibria. The results show that all of the species measured exist mostly as dimers at concentrations >0.01 M typical of most organic synthesis reactions and physical measurements. NMR measurements show that the enols of 1 and 2, which can undergo intramolecular hydrogen bonding, predominate in both THF and DMSO solutions, whereas 3, whose enols cannot be so stabilized, is mostly keto in THF but approximately equimolar enol and keto in DMSO. Dimerization of the monolithium salts is rapid on the NMR time scale but that of the dilithium salts is slow.

Aggregation and reactivity of the cesium enolate of 6-phenyl-alpha-tetralone: comparison with the lithium enolate.

The cesium enolate of 6-phenyl-alpha-tetralone (CsPAT) has a lambda(max) in THF at about 387 nm, but the variation with concentration is too small for application of singular value decomposition. Proton-transfer studies with several indicators show that CsPAT forms monomer-tetramer mixtures with a tetramerization equilibrium constant, K(1,4) = 2.3 x 10(11) M(-3). The pK of the monomer is 23.39 on a scale where fluorene is assigned 22.9 (per hydrogen). For comparison, the lithium enolate, LiPAT, is also a monomer-tetramer with K(1,4) = 4.7 x 10(10) M(-3) and a monomer pK = 14.22. HMPA in large amounts promotes dissociation to monomer with both enolates. Ion-pair S(N)2 initial rates were measured for CsPAT with several alkyl halides and with methyl tosylate and compared with other rates with LiPAT. In all cases, the enolate monomers are much more reactive than the aggregates. Reaction of CsPAT with alkyl halides is generally C-alkylation but HMPA promotes increasing amounts of O-alkylation. A new indicator, 11-methyl-11H-benzo[b]fluorene, has a pK on the cesium scale of 23.39.

Aggregation and reactivity of the dilithium and dicesium enediolates of 1-naphthylacetic acid.

UV-vis spectra of the dilithium, 1-Li, and dicesium, 1-Cs, enediolates of alpha-naphthylacetic acid show no systematic change with concentration in dilute THF solution, but addition of small amounts of HMPA causes a bathochromic shift in the spectrum of 1-Li. These results indicate that these salts are aggregated and that HMPA breaks up the aggregates of 1-Li. The quantitative effect of small increments of HMPA indicates that 1-Li is a dimer. Alkylation reactions of 1-Cs show half-order kinetics in enediolate indicating that this salt is also dimeric but that the small amount of monomer in equilibrium is the actual reactant. Alkylation of 1-Li, however, is much slower and shows first-order kinetics interpreted as a direct reaction of the dimer; the amount of monomer in this case is too small to compete. A solution of 1-Li in THF containing 10% HMPA is much more reactive in alkylation than 1-Li alone and the first-order dependence in 1-Li is now interpreted as reaction of the monomer. Compound 1-Li is found to form a mixed aggregate with LDA, a finding that has possible synthetic significance since enediolates used in syntheses are frequently prepared using LDA. Structures of these compounds are suggested based on model ab initio computations.

A computational study of lithium enolate mixed aggregates.

Ab initio calculations were performed to examine the formation of mixed dimer and trimer aggregates between the lithium enolate of acetaldehyde (lithium vinyloxide, LiOV) and lithium chloride, lithium bromide, and lithium amides. Gas-phase calculations showed that in the absence of solvation effects, the mixed trimer 2LiOV.LiX is the most favored species. Solvation in ethereal solvents was modeled by a combination of specific coordination of dimethyl ether ligands on each lithium and "dielectric solvation" (DSE, dielectric solvation energies), immersion of each molecule in a cavity within a continuous dielectric having the dielectric constant of THF at room temperature. DSE is less important for aggregates (reduced dipoles or quadrupoles) than monomers (dipoles) and is also reduced for the coordinatively solvated species. Both solvation terms reduce the exothermicity of aggregation. In many cases, lithium salts that are three- rather than four-coordinate have significant populations at room temperature. The strongly basic lithium amides prefer mixed aggregates with weaker bases than homoaggregates. The computational results are consistent with the limited experimental data available.

Basicity of a stable carbene, 1,3-di-tert-butylimidazol-2-ylidene, in THF.

The basicity of 1,3-di-tert-butylimidazol-2-ylidene (1) was measured in THF against three hydrocarbon indicators. Both ion pairs and free ions were found and the corresponding equilibrium constants were measured. Homoconjugation was not found in either THF or DMSO. The carbene is effectively more basic in DMSO by several pK units, probably because of hydrogen bonding of 1-H(+) to DMSO. Model ab initio computations are consistent with these results.

Equilibrium constants and alkylation kinetics of two lithium enolates/LiHMDS mixed aggregates in THF.

[reaction: see text] Mixed aggregates between lithium enolates and lithium hexamethyldisilazide (LiHMDS) have been studied in THF using UV-vis spectroscopy. The equilibrium constants (K(agg)) between monomeric LiEn and monomeric LiHMDS are 760 and 560 M(-1) when LiEn are LiSIBP and LiBnPAT, respectively. The alkylation kinetics of the reactions with benzyl bromide were studied at 25 degrees C. The rate constants for the mixed aggregates, k(Mixed), are substantially smaller than those of the monomeric enolates.