Non-Aqueous Titration

Abstract

Acids and bases have long been defined as substances that, when dissolved in water, furnish hydrogen and hydroxyl ions, respectively. This definition, introduced by Arrhenius, fails to recognize the fact that properties characteristic of acids or bases may also be developed in other solvents. A more generalized definition is that of Brönsted, who defined an acid as a proton donor, and a base as a proton acceptor. Even broader is the definition of Lewis, who defined an acid as any material that will accept an electron pair, a base as any material that will donate an electron pair, and neutralization as the formation of a coordination bond between an acid and a base. The apparent strength of an acid or base is determined by the extent of its reaction with a solvent. In aqueous solution all strong acids appear equally strong because they react with the solvent to undergo almost complete conversion to hydronium ion (H 3 O +) and the acid anion. In a weakly protophilic solvent such as acetic acid, the extent of formation of the acetonium ion (CH 3 COOH 2 +) due to the addition of a proton provides a more sensitive differentiation of the strength of acids and shows that the order of decreasing strength for acids is perchloric, hydrobromic, sulfuric, hydrochloric, and nitric. Acetic acid reacts incompletely with water to form hydronium ion and is, therefore, a weak acid. In contrast, it dissolves in a base such as ethylenediamine, and reacts so completely with the solvent that it behaves as a strong acid. This so-called levelling effect is observed also for bases. In sulfuric acid almost all bases appear to be of the same strength. As the acid properties of the solvent decrease in the series sulfuric acid, acetic acid, phenol, water, pyridine and butylamine, bases dissolved in them become progressively weaker and the differences between bases are accentuated. In order of decreasing strength, strong bases of value for non-aqueous titrations are potassium methoxide, sodium methoxide, lithium methoxide, and tetrabutylammonium hydroxide. Many water-insoluble compounds acquire enhanced acidic or basic properties when dissolved in organic solvents. Thus the choice of the appropriate solvent permits the determination of a variety of such materials by non-aqueous titration. Further, depending upon which part of a compound is physiologically active, it is often possible to titrate that part by proper selection of solvent and titrant. Pure compounds can be titrated directly, but it is often necessary to isolate the active ingredient in pharmaceutical preparations from interfering excipients and carriers.