Acidity of Anilines: Calculations vs Experiment

Abstract

The gas-phase acidities of ca. 60 monosubstituted anilines (with acidity span of almost 50 kcal mol(-1)) have been calculated using density functional theory (DFT) at the B3LYP/6-311+G** level. At this relatively simple level of theory the calculated (ΔG(calc)) and available experimental (ΔG(exp)) acidities are in reasonable quantitative correlation according to the following equation: ΔG(obs) = a + bΔG(calc), where a=20.79, b=0.942, n=27, R(2)=0.990, and s=0.78 kcal·mol(-1). The slope is not far from its ideal value. Substituent effects on the acidities were dissected separately into those operating in the neutral acid molecule and in its conjugated anion using the isodesmic homodesmotic reactions. All in all, both forms, neutral and anionic, are contributing in combination to make up the gross acidity of anilines. However, the contributions of the anions into the gross substituent effects are much larger than the substituent effects in the neutral anilines. Some of the systems were used in testing a relatively new theoretical model, COSMO-RS (conductor-like screening model for real solvents), using it for the prediction of pK(a) values in DMSO. The method proved to be rather accurate for showing pK(a) trends (R(2)=0.980 in DMSO). However, the predicted absolute pK(a) values were all somewhat lower (rmsd=2.49 kcal·mol(-1)) than the respective experimental values.

Fluoro‐ and Perfluoralkylsulfonylpentafluoroanilides: Synthesis and Characterization of NH Acids for Weakly Coordinating Anions and Their Gas‐Phase and Solution Acidities

“…31. In our work, we have focused on calculating p K a values in DMSO and MeCN solutions 28s. 32 As a standard for the ab initio p K a calculations, combinations of high quality GA calculations or experimental values with continuum solvent models33 were applied.…”

Calculations of pKa Values of Selected Pyridinium and Its N-Oxide Ions in Water and Acetonitrile

“…Up to now, numerous attempts have been undertaken to calculate pK a values by means of the direct method showing good performance for a few classes of compounds, like This scheme was prepared based on a known cycle which could be found elsewhere. 69,72 The carboxylic acids, 70,71,77,80 alcohols, 81 phenols, 82 pyridines, 66 amines, 83 anilines, 84 uracils, 85 and lately sugars. 86 On the other hand, it has also been shown by Kelly et al 72 that this procedure may fail to give a good pK a correlation between experimental and computational results for weak acids and other classes of compounds.…”

Theoretical study of substituent effects on the gas‐phase stabilities of phenoxide anions

“…The total substituent effects obtained by Eqn (6) can be separated to the substituent effects of ions and their corresponding neutral species . This kind of separation has been attempted to various ionic systems such as phenoxide anions, benzyl anions, anilide anions, benzoate anions, bicyclo[2.2.2]octane‐1‐carboxylate anions, pyridinium ions, anilinium ions, and so on, which always concludes that ionic form contributes most of the total substituent effects. This can be also confirmed by geometrical variations of the present phenoxide anions and their corresponding phenols.…”