Activation energy tetrahydrofuran

The physical properties of the anhydrate form and two polymorphic monohydrates of niclosamide have been reported [61], The anhydrate form exhibited the highest solubility in water and the fastest intrinsic dissolution rate, while the two monohydrates exhibited significantly lower aqueous solubilities. In a subsequent study, the 1 1 solvates of niclosamide with methanol, diethyl ether, dimethyl sulfoxide, N,/V -dimethyl formamide, and tetrahydrofuran, and the 2 1 solvate with tetraethylene glycol, were studied [62], The relative stability of the different solvatomorphs was established using desolvation activation energies, solution calorimetry, and aqueous solubilities. It was found that although the nonaqueous solvates exhibited higher solubilities and dissolution rates, they were unstable in aqueous media and rapidly transformed to one of the monohydrates. 

Under optimum reaction conditions (See Table IV.), selectivity to linear dimer is controlled by the choice of temperature, solvent and tertiary phosphine. Toluene and tetrahydrofuran are the best solvents. Temperatures between 25 to 60 C with a triphenyl or tributylphosphine/palladium acetate catalyst give linear dimer selectivities in the 80 s. At 25 C in toluene, a palladium acetate/tributylphosphine catalyst gave 98.7% conversion and 89.6% linear, 4.7% branched, 1.9% cyclic, and 3.8% heavies selectivity. The linear dimerization reaction was second order in diene with a 3.6 Kcal/mole activation energy. 

Studies have also been carried out in systems containing excess BF3 (17,18). The results (18) show that when the base is dimethyl ether, anisole, tetrahydrofuran, or pyridine, the exchange of BF3 is rapid and probably proceeds through an electrophilic displacement reaction in which the excess BF3 attacks the complex. These reactions all have activation energies of less than 10 kcal/mole, eliminating the possibility of a dissociation process. The data available, however, do not allow a complete evaluation of the reaction mechanism. Studies carried out on BF3-methanol complexes by 19F NMR (17) indicate displacement reactions having an activation energy of 5.3 kcal/mole. 

The isotopic exchange reactions of HNF with DtO and with CFsCOOD have been investigated in tetrahydrofuran-d8 solution at low temperatures using NMR techniques. The former exchange is first order with respect to HNFt and zero order with respect to DgO. The latter exchange proceeds by this same path plus a second-order path. Both exchange reactions were studied at several temperatures, and the activation energies were determined. 

The formulation of two types of ion-pair is an attractive hypothesis which has been used for other systems [130] to explain differences in reactivity. The polymerization of styrene-type monomers in ether solvents, all of which solvate small cations efficiently, seems to be a particularly favourable case for the formation of thermodynamically distinct species. Situations can be visualized, however, in which two distinct species do not exist but only a more gradual change in properties of the ion-pair occurs as the solvent properties are changed. These possibilities, together with the factors influencing solvent-separated ion-pair formation, are discussed elsewhere [131, 132]. In the present case some of the temperature variation of rate coefficient could be explained in terms of better solvation of the transition state by the more basic ethers, a factor which will increase at lower temperatures [111]. This could produce a decrease in activation energy, particularly at low temperatures. It would, however, be difficult to explain the whole of the fep versus 1/T curve in tetrahydrofuran with its double inflection by this hypothesis and the independent spectroscopic and conductimetric evidence lends confidence to the whole scheme. 

The values both in tetrahydrofuran and tetrahydropyran are of the same order of mj itude as those of polystyrene compounds at 25°C. Only the lithium compound of a-methylstyrene has an appreciably higher than that of styrene. The free anion rate coefficient, 830 1 mole" sec" (extrapolated, 25°C A = 1.5 x 10 , E = 7.2 kcal mole" ) [145] is smaller than for styrene, as are the ion-pair coefficients, but the ratio between the two is roughly the same. A major factor producing low rates appears to be a higher activation energy than is found for styrene polymerization. 

The activation energy of anionic propagation in the homopolymerization of styrene was determined to be about 1 kcal. per mole. This value refers to the reaction proceeding in tetrahydrofuran solution. The activation energy for the same reaction in dioxane was reported (1, 2) to be 9 3 kcal. per mole. This is one of many examples which stresses the importance of a solvent in ionic polymerization. 

The activation energy for exchange appears to be lower than that for Grignard substitution. The exchange is more pronounced in tetrahydrofuran than in diethyl ether. Although frequently, the exchange is of no consequence, it can significantly alter final product distribution in some sterically constrained systems. 

Perhaps more important, however, are the initial studies of Van Beylen and his collaborators on the dynamics of dissociation of carboanionic species studied by the technique of electric field relaxation. With fluorenyl lithium in pure diethyl ether and added traces of tetrahydrofuran the overall rate constant for dissociation displays a negative activation energy, strongly suggesting that dissociation does not occur directly from contact on tight ion pairs, which are present in vast excess, but rather via a small number of solvent-separated species. This is important because under identical conditions loose ion pairs cannot be detected spectroscopically. Similarly, with polystyryl caesium in tetrahydrofuran the results point to the presence of a small concentration of loose ion pairs and seems to support the hypothesis of Lohr and Schulz. 

Preparation and Chemical Properties. The saline hydrides are prepared by direct interaction at 300-700°. For complete reaction of lithium, the temperature must be approximately 725°. Sodium normally reacts with H2 only above 200° and the reaction is slow owing to formation of a coating of an inert hydride. However, studies on continuously clean surfaces50 show that the reaction obeys first-order kinetics with an activation energy of ca. 70kJmol 1. Dispersion of sodium in mineral oil increases the reactivity, but NaH in a very reactive form can be prepared at room temperature and pressure by interaction of H2 with sodium and naphthalene (Na+CI0Hg ) in tetrahydrofuran, with titanium isopropoxide as catalyst.51... 

The C-0 and C-C bond lengths in tetrahydrofuran (oxolan) are 142.8 and 153.5 pm, respectively. These values are close to the corresponding bond lengths in dialkyl ethers. The ring is virtually strain-free, but not planar. There are 10 twist and 10 envelope conformations which interconvert rapidly through pseudorotation (activation energy 0.7 kJ mol ). This results in a molecule which has almost free conformational mobility (see p 68). 

The bond lengths in thiolane (tetrahydrothiophene) are the same as those in dialkyl sulfides. As in tetrahydrofuran (see p 67), the ring is nonplanar and conformationally flexible. The twist conformation is, however, preferred because of the larger heteroatom. The activation energy for pseudorotation is greater than that for tetrahydrofuran. The chemical shifts in the NMR spectrum correspond to those observed for cycloalkanes and dialkyl sulfides. 

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