Yehuda Yanuka

Spectroscopic studies on caffeine and isocaffeine

Abstract UV and NMR spectra of caffeine and Isocaffeine were measured in three solvents of different polarity. The Information so obtained revealed unique differences in the electronic structure of 7- and 9- alkyl substituted xanthines. 9-Methyl derivatives bear a “soft” nitrogen at position 3; in 7-methylxanthines this nitrogen is rather “hard”. This characteristic distinction is explained on the basis of orbital interactions, which are also responsible for self-association. In the process of self-association. isocaffeine and caffeine share a hydrophobic effect, but in caffeine water bridges play a decisive rote in molecular aggregation. In contrast, in isocaffeine high polarisability makes the most important contribution to self-association. Steric interference between 3- and 9-alkyl substituents or between a 9-methy1 and a 3-NH group, proposed earlier, does not explain satisfactorily the properties of these xanthines.

Stereospecific epimerization, oxidation and toxine rearrangement in cinchona alkaloids catalyzed by acetic acid

Abstract Glacial acetic acid catalyzed a novel stereospecific epimerization of chinchona alkaloids at C - 9. In the presence of water, acetic acid also catalyzed the known toxine rearrangement and oxidation to the corresponding 9- keto derivatives. Addition of acetic anhydride to acetic acid diminished oxidation and epimerization at C-9, and the main products were the results of hydramine fission. Only propionic acid but not other acids, effected similar but not identical transformations. Addition of small quantities of H 2 O 2 or exclusion of oxygen produced quantitative oxidation and rearrangement products, respectively. The catalysis by aqueous solutions of acetic acid, involves C-9-OH in the formation of a three-membered ring intermediate. On the other hand,with anhydrous acetic acid, the acetoxyl at G-9 participates in construction of a five-membered ring intermediate. In both cases the reaction appears to be intramolecular. Support for the proposed mechanisms was provided by the isolation of a quarternary salt derived from quinidine, the structure of which was also characterized by X-ray diffraction analysis. Aqueous acetic acid catalyzed the rearrangement of this salt to its corresponding toxine only . and neither oxidation nor epimerization could be observed under conditions employed for the natural alkaloids.