Steric Inhibition Of Solvation Research Articles

Inductive vs Solvation Effects in Primary Alkyl Amines: Determination of the Standard Potentials

The determination of the standard potential of alkyl primary amines is reported for the first time using the nanosecond equilibrium method. The versatility and accuracy of the method demonstrates that it is not only an alternative to the classical and modern electrochemical methods, but also a powerful tool for quantifying inductive and/or solvation effects in a related family of compounds. Two different trends were observed depending on alkyl chain length. For "short-chain" alkyl primary amines, where the solvation around the amino group is expected to be the same, the standard potential value appears to follow a linear relationship with the number of carbon atoms, which indicates that the methylene group (-CH2-) causes an inductive effect that is responsible for the stabilization of the amine cation radical. Meanwhile, the E(o) rises slightly to a constant potential value 1.500 V for "long-chain" unbranched alkyl primary amines. This interesting result can be explained by a steric inhibition of solvation around the amino group due to a fold of the long alkyl chain following a solvent exclusion mechanism.

Protonation of alkylpyridines: polarizability and steric effects in the base and in the cation

AbstractThe energies of alkyl‐substituted pyridines in the 2‐, 3‐, 4‐ and 2,6‐positions, of their protonated forms and of reference derivatives of benzene were calculated at the RHF/6–31G(d,p) and B3LYP/6–31G(d,p) levels. The results were processed by isodesmic reactions, expressing the substituent effect separately for the base molecules, their protonated forms and for the gas‐phase basicity. The substituent effect is greatest in the protonated forms, and in the uncharged bases it is approximately three times smaller. In both cases, it is stabilizing: basicity is given by the difference. No actual steric effect was revealed, merely a stabilizing effect in the 2‐position, which can be explained in terms of polarization. This effect is almost equal in the protonated and unprotonated forms, so that it is not operative in the basicity. In water solution, all effects are attenuated and steric inhibition of solvation appears, particularly with 2,6‐di‐tert‐butylpyridine and 2,6‐diisopropylpyridine. Copyright © 2001 John Wiley & Sons, Ltd.

ChemInform Abstract: Gas-Phase and Solution Basicities of Some Alkyl 2,6-Dialkylphenyl Ketones: A Comparative Analysis.

Abstract The gas-phase basicity of a number of alkyl 2,6-dialkylphenyl ketones (2,6-R2C6H3COR′) has been found to be almost insensitive to structural variations, as a result of a compensation of steric and electronic effects associated with the bulkiness and to the polarizability, respectively, of R and/or R′. On the contrary, the basicity in concentrated sulfuric acid undergoes, along the same series of compounds, a variation of nearly 8 pK units, as a consequence of steric inhibition of solvation of the protonated carbonyl as the main effect played by R and/or R′. The results in the condensed phase agree very nicely with recent findings relevant to some 4-substituted 2,6-dimethylacetophenones and 4-substituted acetophenones as well as with data for a large number of dialkyl or alkyl aryl ketones (either from the literature or determined herein) leading to an overall pKBH+ vs. m∗ correlation (slope=8.8, n=31, r=0.996; Eq. (3) ) which appears to be of general significance and identifies steric inhibition of solvation as a common prevailing factor influencing the carbonyl basicity, at least in the absence of strong conjugative interactions.

Control of peptide conformational preferences by intramolecular ion-pairing: a NMR and molecular mechanics analysis of glycyl-containing dipeptides in aqueous solutions

A NMR and molecular mechanics analysis of isomeric N- and C-terrninal glycyl dipeptides in aqueous solutions is described, with the overall objective of understanding the basis of their different rotameric preferences. The C-terminal glycyl dipeptides are signhicantly more conformationally homogeneous than their N-terminal isomers in all water-containing solvents, as probed by the magnitude of the chemical shift non-equivalence of the diastereotopic glycyl methylene protons in the 1H NMR spectra of both isomers. Further NMR experiments demonstrated that, with both sets of isomers, the degree of conformational homogeneity is under control of the extent of intramolecular ion pairing; the ion pairing is thus a greater conformational determinant in C-terminal glycyl dipeptides. Molecular mechanics studies failed to demonstrate an inherent structural basis for the differences in rotameric preferences between isomers. To explain the differences, it is hypothesized that alkyl substitution of the α-carbon in C-terminal glycyl dipeptides destabilizes the ammonium ion to a greater extent through steric inhibition of solvation than in N-terminal dipeptides, which forces intramolecular ion pairing to occur to a greater extent. The significance of these results towards the de novo prediction of polypeptide tertiary structure in solution is discussed briefly.

ChemInform Abstract: An Analysis of Complex Alkyl‐Substituent Effects in the Water‐Catalyzed Hydrolysis of 1‐Acyl‐1,2,4‐triazoles

Pseudo-first-order rate constants and thermodynamic activation parameters have been determined for the water-catalyzed hydrolysis of the 1-acyl-1,2,4-triazoles 1–9 in water and in aqueous acetonitrile [x(H2O) = 0.80]. The reaction occurs via water-catalyzed nucleophilic attack of water at the amide carbonyl group. Variation of the alkyl group in the acyl part of the substrate led to the sequence of reactivities (in water): R = t-Bu > i-Pr > Et > Me > n-Pr > s-Bu > i-Pent > neo-Pent. This complex behavior strongly suggests the operation of a composite steric effect most likely involving contributions from conformational preference (SEI), change of coordination number at carbonyl carbon (SE2), steric repulsion between O2 and the alkyl group (SE3), and steric inhibition of solvation (SE4). Modelling of the relative rates in water in terms of the expanded branching equation gave satisfactory results. Two possible transition states are proposed for the neutral hydrolysis, one involving intramolecular hydrogen bonding between the second water molecule and N2 of the 1,2,4-triazole ring. The different sequence of reactivities for neutral hydrolysis in aqueous acetonitrile as well as the rates for hydroxide-ion-catalyzed hydrolysis in water (B AC2 mechanism) support the analysis of substituent effects.

An analysis of complex alkyl‐substituent effects in the water‐catalyzed hydrolysis of 1‐acyl‐1,2,4‐triazoles

AbstractPseudo‐first‐order rate constants and thermodynamic activation parameters have been determined for the water‐catalyzed hydrolysis of the 1‐acyl‐1,2,4‐triazoles 1–9 in water and in aqueous acetonitrile [x(H2O) = 0.80]. The reaction occurs via water‐catalyzed nucleophilic attack of water at the amide carbonyl group. Variation of the alkyl group in the acyl part of the substrate led to the sequence of reactivities (in water): R = t‐Bu > i‐Pr > Et > Me > n‐Pr > s‐Bu > i‐Pent > neo‐Pent. This complex behavior strongly suggests the operation of a composite steric effect most likely involving contributions from conformational preference (SEI), change of coordination number at carbonyl carbon (SE2), steric repulsion between O2 and the alkyl group (SE3), and steric inhibition of solvation (SE4). Modelling of the relative rates in water in terms of the expanded branching equation gave satisfactory results. Two possible transition states are proposed for the neutral hydrolysis, one involving intramolecular hydrogen bonding between the second water molecule and N2 of the 1,2,4‐triazole ring. The different sequence of reactivities for neutral hydrolysis in aqueous acetonitrile as well as the rates for hydroxide‐ion‐catalyzed hydrolysis in water (B AC2 mechanism) support the analysis of substituent effects.

ORTHO effects of chloro- and nitrobenzoic acids in water—dimethylsulphoxide mixtures at 25° C

The dissociation of ortho-chloro- and nitro-benzoic acids in water—DMSO mixtures (0.0 + 0.8 DMSO mole fraction) was studied by means of a linear combination of the ordinary polar, proximity polar, and steric effects. Enthalpic and entropic contributions to substituent effects for the ortho-derivatives were also examined. The dissociation of the ortho-chloro-derivatives appear to be mostly anion-controlled. However, for the ortho-nitro-derivatives, the steric inhibition of solvation on the undissociated molecules may also be involved in controlling the course of the reaction.

The transmission of polar effects. Part V. The kinetics of esterification with diazodiphenylmethane and the ionization of substituted acetic and propionic acids in several solvents

The rate coefficients for the reaction with diazodiphenylmethane in methanol, ethanol, isopropyl alcohol,t-butyl alcohol, 2-methoxyethanol, 2-n-butoxyethanol, dimethyl sulfoxide, ethyl acetate, and toluene at 30° and the pKa values in water, 50% ethanol–water, and 80% 2-methoxyethanol–water of 18 substituted acetic and propionic acids have been determined. A further 14 acids have been studied to a more limited extent. The effect of substitution has been estimated by linear free energy relations. The reaction constants for the ionization reaction are almost independent of the medium. This is interpreted as being due to the field effect of the proximate polar substituents passing through the molecular cavity almost alone. The occurrence of steric inhibition of solvation causing acid weakening for bulky multi-substitution is confirmed. The reaction constants for the esterification reaction are affected by the solvent. This is attributed to dependence on solvation of the transition state.

Acid dissociation, UV spectra and hydrolyses of several α-mercapto- and α-alkoxyacetic acids and their ethyl esters

New σ * values of some α-mercapto and α-alkoxy groups have been obtained from the kinetic measurements of acidic and alkaline hydrolyses of ethyl α-substituted carboxylates. The acid dissociation constants and UV spectra of these carboxylic acids are discussed using these newly obtained σ * values. The relative dissociation constants of α-substituted carboxylic acids cannot be accounted for by the polar effects only since the steric inhibition of solvation around the carboxylate ion by α-substituents plays an important role. In addition, the non-bonding interaction between the α-mercapto group and the carboxylate ion appears to be significant.

The separation of polar and steric effects. Part VI. The kinetics of the acid-catalysed esterification of substituted benzoic acids by methanol

Rate coefficients have been determined for the acid-catalysed esterification of benzoic acid and of o-XC6H4·CO2H (X = F, Cl, Br, I, Me, Et, or Pri) by methanol, with toluene-p-sulphonic acid as catalyst, at several temperatures. The acids m-XC6H4·CO2H (X = Cl, Me, or NO2) have been similarly studied at 60°, and approximate rate coefficients have been determined for the esterification of o-t-butylbenzoic acid at 100 and 120°.Arrhenius parameters and the related quantities of transition-state theory have been evaluated for the reactions of the ortho-substituted acids. The effect of ortho-substitution on the entropy of activation (ΔS‡) in esterification is discussed in terms of a ‘bulk effect’ which tends to decrease ΔS‡, and steric inhibition of solvation of the transition state which tends to increase ΔS‡. All the ortho-substituents studied (except t-butyl) depress the enthalpy of activation (ΔH‡) relative to that for the reaction of the parent acid and two effects are tentatively suggested to account for this, namely, the secondary steric effect of ortho-substituents, and a steric inhibition of ‘ring solvation’ of the initial state, which may be brought about by substituents in any position in the ring.Taft steric substituent constants (Es) have been evaluated for the ortho-substituted acids, and these are compared with values obtained from other systems. The differences found are discussed in terms of the Hammett reaction constant (ρ) and of the nature of the solvent.It is also concluded that results from the kinetics of esterification cannot replace those from acid-catalysed ester hydrolysis for the purpose of accurately satisfying the conditions of the Taft relation.

Acidity functions in strongly basic meida. Part III. The ionisation of pentamethylphenol in methanolic sodium methoxide solutions and the inference of steric inhibition of solvation from acidity function data

The ionisation of pentamethylphenol in concentrated methanolic sodium methoxide solutions parallels an H– acidity function which deviates less from ideality than the corresponding function deduced from the ionisation of t-butyl phenols. The results are consistent with the possibility that steric inhibition of solvation of the phenol anions by bulky ortho substituents is reflected not only in the acid ionisation constants of the phenols but also in the variation of acidity functions with sodium methoxide concentration.

Ionic dissociation of 4-substituted 2,6-dimethylphenols

The pK values of 4-X-2,6-dimethylphenols (X = Me, MeO, H, F, Br, MeCO, CN, CHO, NO2, and NO) have been measured in water, at 25°, by potentiometric titration. For dissociation of 2,6-dimethylphenols, ρ is 21% larger than the value for phenols, and this is attributed to steric inhibition of solvation in the 2,6-dimethylphenoxide anions. The pK value of 4-nitroso-2,6-dimethylphenol suggests that it exists in aqueous solution as the monoxime of 2,6-dimethylbenzoquinone.

Influence des solvants sur la transition n → π * des cétones saturées

It has been found that the positions of absorption maxima (ν s ) of the n → π * transition in the 33000–38000 cm −1 region for ketones in various solvents are also dependent on the structure of the ketone. The authors found that M acR ae's formula cannot be applied directly to the experimental observations without introducing serious restrictions as to generality. Their study based on the specific properties of a ketone series for a solvent coupled with a linear free energy postulate permits the development of an excellent description of these absorption maxima in terms of the nature of the solvent and of the structure of the ketone. This work has been carried out for eight aliphatic ketones (Me CO Me, Me CO Pr, Me CO i Bu, Pr CO Pr, Me CO neoPe, Pr CO neoPe, tBu CO neoPe and tBu CO tBu) in fourteen solvents (hexane, benzene, cyclohexane, isooctane, dioxane, diethyl ether, tetrahydrofuran, dimethyl-formamide, acetonitrile, chloroform, t-butyl alcohol, ethanol, methanol and water). The correlations ν s = f(ν H ), which relate the behavior of the ketone series in various solvents to their comportment in hexane, permit a meaningful generalized description of the solute-solvent system. All of the solvents, including water, may be described by a linear expression of the form ν s = A s ν H + B s . Numerical values of A s and B s have been calculated for the fourteen solvents investigated. A more refined treatment makes it possible to isolate the influence of the solvent on the n → π * transition of this series of ketones by means of the following equation ν s - ν H = F(ν H - ν I ) ν I = 33370 cm −1 which is applicable to all of the cases studied except water. The values of the parameter F of all the solvents are compared with the known G and Z spectroscopic functions. Furthermore this expression points to the existence of ketones for which ν s will be constant in different solvents and suggests therefore a certain steric inhibition of solvation.