Potentiometric titrations can be carried out in chlorobenzene by using glass and sleeve-type calomel electrodes and a Beckman Model GS pH Meter. Acetous erchloric acid is the most suitable titrant. Galvanometer response is rapid ancfno erratic galvanometer needle deflections are noted when this titrant is used. The optimum concentration of titrant at the end point appears to be approximately 20 parts titrant for every 100 parts of solution. Bases as weak as caffeine can be determined in this solvent but only with a limited de ree of accuracy. A mixed solvent containing 20 per cent glacial acetic acid in cffiorobenzene can be used for the titration of organic bases insoluble in chlorobenzene. Bromopheool blue is a suitable indicator for use in chlorobenzene. Neutral red, brilliant green, and methyl red can also be used in this solvent but indicator changes are not as satisfactory as with bromophenol blue.
WENTY-FIVE YEARS ago, Conant, Hall, and T W ~~~~ (1-3) showed that many substances which exhibit no basic properties in water behave as relatively strong bases in glacial acetic acid. The analytical significance of their observations was not immediately realized and the technique of acid-base titrations in nonaqueous solvents was not generally accepted until after the second world war. The distinct advantage of this method, as compared with volumetric procedures camed out in aqueous media, made it particularly suited to the quality control of pharmaceuticals. The application of acid-base titrations to the analysis of pharmaceutically important compounds has been adequately reviewed by Pifer, Wollish, and Schmall (4). Reviews of a more general nature have been published by Riddick (5-7) and Ballczo (8, 9).
Research in this field has followed the pattern laid down by Conant, Hall, and Werner. The "super acids" appeared to offer the ultimate in base intensification and solubilization. A large number of papers, therefore, appeared in the literature dealing with the analysis of various organic bases in glacial acetic acid. It soon became evident that other solvents were superior to glacial acetic acid both in solubilizing ability and in base-strengthening power. Pifer, Wollish, and Schmall (10) showed that the addition of aprotic solvents to glacial acetic acid greatly increased the magnitude of the potential break at the end point in the potentiometric titration of very weak bases with acetous perchloric acid. Fritz (11) reported that many solvents gave as good or better results than did glacial acetic acid. Chlorobenzene can be classified as an inert or *