Beilstein J. Org. Chem.2016,12, 1493–1502, doi:10.3762/bjoc.12.146
, triethyl orthoformate and two equivalents of diphenylphosphine oxide. The method is also suitable for the preparation of (aminomethylene)bisphosphonates using (MeO)2P(O)H/(MeO)3CH or (EtO)2P(O)H/(EtO)3CH reactant pairs and even secondary amines. Several intermediates referring to the reaction mechanism
together with a few by-products could also be identified.
Keywords: (aminomethylene)bisphosphine oxides; (aminomethylene)bisphosphonates; microwave; three-component condensation; Introduction
Substituted (hydroxymethylene)bisphosphonic acid derivatives form an important group of drugs used in the
antibacterial, antiparasitic, anticancer and herbicidal activities [5].
(Aminomethylene)bisphosphonates may be prepared in different ways [5]. One of the most convenient and widespread methods is the three-component condensation involving an amine, an orthoformate and a dialkyl phosphite. Usually, primary or
PDF
Graphical Abstract
Scheme 1:
Proposed routes for the three-component condensation [7].