Origin of the Acidity Enhancement of Formic Acid over Methanol:  Resonance versus Inductive Effects

Abstract

Density functional theory calculations were employed to study the relative contribution of resonance versus inductive effects toward the 37 kcal/mol enhanced gas-phase acidity (DeltaH degrees (acid)) of formic acid (1) over methanol (2). The gas-phase acidities of formic acid, methanol, vinyl alcohol (5), and their vinylogues (6, 8, and 9) were calculated at the B3LYP/6-31+G level of theory. Additionally, acidities were calculated for the formic acid and vinyl alcohol vinylogues in which the formyl group and the vinyl group, respectively, were perpendicular to the rest of the conjugated system. Comparisons among these calculated acidities suggest that inductive effects are the predominant effects responsible for the enhanced acidity of formic acid over methanol, accounting for between roughly 62% and 65% of the total enhanced acidity; the remaining 38% to 35% of the acidity enhancement appears to be due to resonance effects. Further comparisons suggest that resonance effects are between roughly 58% and 65% of the 26 kcal/mol calculated acidity enhancement of vinyl alcohol over methanol, and the remaining 42% to 35% are due to inductive effects.

Formic Acid, a Novel Metabolite of Chronic Ethanol Abuse, Causes Neurotoxicity, Which Is Prevented by Folic Acid

“…(1980) showed profound CSF anion gap metabolic acidosis in alcoholic patients. Our data showing the presence of FA in CSF may indeed explain (Holt and Karty, 2003) the observed acidosis.…”

Acidities of Nitrous and Nitric Acids

“…The relatively strong acidity of carboxylic acids has always been evaluated with alcohols as a natural reference 3,6–11. By the same token, a reference compound for nitrous acid is a hydroxylamine derivative.…”

“…An alternative theory was suggested first for carboxylic acids3 and then extended to nitrous and nitric acids:4,5 the origin of the acidity is seen in the charge distribution and in the electrostatic potential of the uncharged molecules of the acids. In the case of carboxylic acids, the problem raised a vivid discussion6–11 and complete agreement has not yet been reached. In our opinion, the problem can be rationalized (and for the greater part solved) if it is divided into two independent questions:7,10…”

Fundamentals of Organic Chemistry

“…43 They assessed the resonance contribution toward the enhanced acidity of carboxylic acids by comparing the DPEs of a series of conjugated hydroxyaldehydes in their planar (12) versus perpendicular (13) conformations. (3.3), another equation is needed in order to solve for the values of these contributions.…”