Microwave-assisted hydrolysis of phosphonate diesters: an efficient protocol for the preparation of phosphonic acidsElectronic supplementary information (ESI) available. See DOI: 10.1039/c2gc35547g

• Main Authors: Jansa, Petr, Baszczy ski, Ond ej, Procházková, Eliška, Dra ínský, Martin, Janeba, Zlatko
• Format: Journal Article
• Language: English
• Published: 01.08.2012
• ISSN: 1463-9262; 1463-9270
• DOI: 10.1039/c2gc35547g

A new highly efficient method for the hydrolysis of acyclic nucleoside phosphonate diesters (or generally of any organophosphonates) to the corresponding phosphonic acids has been developed. This novel methodology employs inexpensive hydrochloric acid in equimolar amounts to the number of ester groups present in the molecule and thus, avoids using trimethylsilyl halogenides, the standard reagents for these types of transformations. Moreover, simple and easy work-up of the reaction mixture affords very clean products in high yields (usually 77-93%). Another advantage of the described hydrolysis of phosphonate diesters is the fact that the course of the reaction can be instantly monitored through pressure changes in the reaction vessel. This 'green' method has also been successfully used for the preparation of otherwise synthetically difficult to access (phosphonomethoxy)ethyl (PME) derivatives of guanine (PMEG) and hypoxanthine (PMEHx), and furthermore, the method gains access to important novel acyclic nucleoside phosphonates derived from 2-chlorohypoxanthine and from xanthine ( e.g. PMEX). A highly efficient MW-assisted hydrolysis of phosphonate diesters to the corresponding phosphonic acids using aqueous HCl has been developed.