Synthesis and characterization of hydrophilic theophylline base compounds and their use as ligands in the microwave assisted Suzuki–Miyaura couplings of halopyridines in water

Xanthine derivatives, caffeine (L1), theobromine (L2), theophylline (L3), 7-(β-hydroxyethyltheophylline) (L4), (7-(2,3-dihydroxypropyl)theophylline) (L5), and theophylline 7-acetic acid (L6) and the acetylated derivatives of the later three (L7–L9) were employed as ligands for the in situ palladium catalyzed Suzuki–Miyaura cross couplings of a series of halogenated pyridines. Optimized conditions were found where the diacetylated ligand (L8) was determined to be the best for this process, producing good to excellent yields in the couplings of halogenated anilines with phenylboronic acid under mild reaction conditions in water using microwave irradiation.