The apparent lipophilicity of quaternary ammonium ions is influenced by Galvani potential difference, not ion pairing. A cyclic voltammetry study.

PURPOSE: This work examines whether ion-pairing contributes to the apparent lipophilicity of cations, which is seen by a shake-flask or titrimetic method to be influenced by the nature and concentration of counter-ions. METHODS: To solve this problem, the lipophilicity of several quaternary ammonium drugs was measured by cyclic voltammetry in the 1,2-dichloroethane/water system. The standard ionic partition coefficient values so obtained (log Pdce(o,C)) were correlated with log Poct values calculated by the CLOGP algorithm for the respective neutral molecules. RESULTS: The standard (i.e., intrinsic) lipophilicity values are shown to depend on a, the structure of the ion (nature, volume, charge), and b, on the Galvani potential difference at the ITIES (interface between two immiscible electrolyte solutions). CONCLUSIONS: The standard lipophilicity values were not influenced by counter-ions. In contrast, simulations showed that the increased apparent lipophilicity of cations, as measured by the shake-flask method in the presence of lipophilic anions, is fully accounted for by the resulting increase in the Galvani potential difference

Selenium-containing heterocycles from isoselenocyanates: synthesis of 1,3-selenazoles from N-phenylimidoyl isoselenocyanates

The reaction of N-phenylbenzamides 5 with excess SOCl2 under reflux gave N-phenylbenzimidoyl chlorides 6, which, on treatment with KSeCN in acetone, yielded imidoyl isoselenocyanates of type 2. These products, obtained in almost quantitative yield, were stable in the crystalline state. They were transformed into selenourea derivatives 7 by the reaction with NH3, or primary or secondary amines. In acetone at room temperature, 7 reacted with activated bromomethylene compounds such as 2-bromoacetates, acetamides, and acetonitriles, as well as phenacyl bromides and 4-cyanobenzyl bromide to give 1,3-selenazol-2-amines of type 9 (Scheme 2). A reaction mechanism via alkylation of the Se-atom of 7, followed by ring closure and elimination of aniline, is most likely (cf. Scheme 7). In the case of selenourea derivatives 7d and 7l with an unsubstituted NH2 group, an alternative ring closure via elimination of H2O led to 1,3-selenazoles 10a and 10b, respectively (Schemes 4 and 7). On treatment with NaOH, ethyl 1,3-selenazole-5-carboxylates 9l and 9s were saponified and decarboxylated to give the corresponding 5-unsubstituted 1,3-selenazoles 12a and 12b (Scheme 6). The molecular structures of selenourea 7f and the 1,3-selenazoles 9c and 9d have been established by X-ray crystallography (Figs. 1 and 3)