E. Dabrowska, A. Burzyńska, A. Mucha
Nov 1, 2009
Citations
0
Influential Citations
38
Citations
Journal
Journal of Organometallic Chemistry
Abstract
Three-component reaction of a primary amine, diethyl phosphite and triethyl orthoformate followed by acid hydrolysis of the adduct provides N-substituted aminomethylenebisphosphonic acids in good yields. Being extremely versatile, it is commonly utilized for preparation of compounds possessing potential antiosteoporotic, antibacterial, anticancer, antiparasitic or herbicidal activity. However, the mechanism of the reaction remains unknown. p-Nitroaniline has been found an interesting tool to shed light on this matter. Its use allowed to separate and identify four intermediates, both non-phosphorus and phosphorus containing, and subsequently suggest the mechanism of the whole process. The acquired knowledge was helpful in explanation the route and the final product structure obtained for more complex reaction proceeding with the use of 4-aminopyridine. Additional alkylation of the pyridine nitrogen atom, leading to unexpected N-(1-alkylpyridinium-4-amino)methylenebisphosphonic acids was unambiguously proved.