Intramolecular monodealkylation during the attempted synthesis of diethylphosphonoacetohydroxamic acid

The reaction of diethyl methyl phosphonoacetate ( 1 ) with hydroxylamine in NaOH solution resulted in the loss of one of the phosphorus ethyl groups, and yielded monoethylphosphonoacetohydroxamic acid ( 2 ) as the major product (79%) and diethylphosphonoacetic acid ( 3 ) as the minor product (21%). A series of control experiments were carried out to elucidate the sequence of the reactions leading to 2 . When the reaction of 1 with NH₂OH was carried out in NaHCO₃ solution, a transient product 4 was also observed, which slowly transformed to 2 . Compound 4 was assigned the structure diethylphosphonoacetohydroxamic acid. There was no dealkylation observed at the phosphorus when 1 was reacted with methoxylamine or when O‐methyl diethylphosphonoacetohydroxamate ( 7 ) was placed in alkaline solution. The dealkylation at phosphorus was interpreted in terms of intramolecular nucleophilic catalysis by the hydroxamic OH group attacking the phosphorus in 4 , involving cyclic 1,2,5‐oxazaphospholidine intermediates. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:67–71, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10082