Intramolecular monodealkylation during the attempted synthesis of diethylphosphonoacetohydroxamic acid

Article abstract of DOI:10.1002/hc.10082

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 monoethylphosphonoaceto-hydroxamic 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 diethylphos-phonoacetohydroxamic 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.