title: An Expeditious Route to Novel 1,4,2-Benzodiazaphosphepin-5-one 2-Oxide Analogues.
abstract: A short and efficient synthesis of the novel 1,4,2-benzodiazaphosphepin-5-one 2-oxide ring system, a phosphonamidate isostere of the 1,4-benzodiazepine-2,5-dione system, has been carried out in good overall yield. The key step is the base-induced cyclization of (2-aminobenzamido)methylphosphonates 6a-c to the 1,4,2-benzodiazaphosphepin-5-one 2-oxides 7a-c. Alkylation of 7b with methyl iodide gives the expected N-methyl analogue 9. When a tandem one-pot cyclization/alkylation is carried out from 6b in the presence of excess base, the sole isolable product obtained is the phosphonate 13, presumably via ethanolysis of a transiently formed 9. Carrying out the tandem cyclization/alkylation in the absence of excess base, however, affords only 9. Thionation of 7 with Lawesson's reagent occurs at either the phosphonamidate oxygen (P-2) or the amide carbonyl (C-5) depending on the steric constraint of the N-4 substituent.
authors.affiliation: Agricultural Products Research Division, American Cyanamid Company, Princeton, New Jersey 08543-0400.
authors.forename: Gary M.
authors.initials: GM
authors.lastname: Karp