Prediction of the strengths of organic acids

Abstract

THE strength of an acid, HA, in water is expressed quantitatively by its pK (= -log K ) value, where K = (H+)(A-)/(HA) the parentheses denoting activities. Often, when experimental results are not available, useful estimates of the approximate thermodynamic pK values of organic acids in water can be made, either from consideration of substituent effects or by analogy with substances of known pK. The present Review shows how such treatments, that have already been discussed for organic bases,l can be applied to organic acids. Except where stated, all experimental pK values are from reference 2. In almost all cases they refer to temperatures within the range 18-25' (usually 25").For convenience, acids are considered under the headings: (1) Aromatic acids ; (a) carboxylic acids, (b) phenols, naphthols, and tropolones, (c) thiophenols, (d) other acids; (2) Aliphatic and alicyclic acids; (a) carboxylic acids, (b) alcohols and aldehydes, (c) thio-acids and -alcohols ; (3) Heterocyclic acids ; (a) carboxylic acids, (b) substituted azoles, (c) hydroxy-compounds.Other types, such as amides, imides, /3-ketones (enolic and ketonic forms), hydroxynaphthaquinones, and aromatic thio-acids, are also dealt with in the Discussion.Representative pK values are given in Table 1, in which the acids are arranged in order of decreasing strength.Qualitatively, the same factors' govern the strengths of acids and bases. At any given temperature, the pK, value of an acid or a base is directly proportional to the free energy change in the ionisation reaction, so that the effect of substituents on pK values can be discussed in terms of factors affecting free energies. These factors are mainly polar, resonance, and steric interacti0ns.l Of these, polar effects are approximately constant for any substituent and cumulative when more than one group is involved, so long as two or more highly polar groups are not attached to the same atom.Resonance contributions often roughly parallel polar effects, whereas steric factors usually vary from one class of reaction to another. Carboxylic acid and phenolic groups are able, both in their ions and in their neutral molecules, to exhibit resonance interaction with the remainder of the molecule. In an amine, on the other hand, the lone pair of electrons on the

Thermodynamics of ester and orthoester formation from trifluoroacetic acid

“…The pK,,'s of aliphatic alcohols, R-CH2-OH, arc described by the empirical relationship (31) Assutning that p* would be the same for RIR2R3C-OH (p*: is known t o be the same for RIR,C(OH)2 (32)), this corresponds t o The pK, of CF3(CH30)2C-OH can now be estimated as 8.8 (using ucl:72: = 2.61 and ucIIJO* = l.S1 (33) …”

Free-energy relationships in coordination chemistry. I. Linear relationships among equilibrium constants

“…Consequently, o in this paper is related to 5 ; o = -F/q = pK -pKo = -0'. These (5 and o f ) and other Hammett sigma factors (14,17,18,32,34) have found application in the comparison of metal ion complex stability with ligand basicity (10,13,(19)(20)(21)(22)35). However, the distinction between the various Hammett sigma factors is often overlooked in these applications.…”

The Selection of Arylamidinourea Antimalarials by Their Predicted Physicochemical Properties

“…In order to ensure that the derived regression equation would be fairly comparable with that of Goodford et aL (1973), the choice was restricted to the 61 compounds available to those authors. However, reliable values of ir and a were not known for all of these, and some of the compounds had ortho substituent groups for which no generally applicable a constants could be assigned (Barlin & Perrin, 1966). Such limitations reduced the number of compounds available to the 41 whose ir: a coordinate positions are plotted in Figure 1.…”