3-substituted 1,2-benzisothiazole-1,1-dioxides/beta-ketoesters: multiple anion synthesis and characterization.

Several commmercially available beta-ketoesters were dilithiated with excess lithium diisopropylamide, (LDA), followed by condensation with methyl 2(aminosulfonyl)benzoate to give intermediates that were not isolated but cyclized to 3substituted 1,2-benzisothiazole-1,1-dioxides (BIDs). The same dilithiated beta-ketoesters were condensed with saccharin, under identical conditions to afford the same products, but usually with less consistent results. In all but one instance involving methyl 2(aminosulfonyl)benzoate, only a single tautomer resulted after recrystallization from ethanol. The successful condensations involving saccharin also gave the same tautomer, but only after several recrystallizations from ethanol. Generally, tetramethylethylenediamine, (TMEDA), improved the yield of products, and it was necessary for the successful condensation of the lithiated ester-sulfonamide with dilithiated alpha-acetyl-gamma-butyrolactone, even though the yield was 36%. When the products were recrystallized from ethanol, and NMR spectra were taken in deuteriochloroform, a consistent single tautomer was obtained, whose structure was further elucidated with representative additional spectra (HMQC and DEPT). Also, an X-ray structure is being sought for a single ylidine tautomer.

Many of the products containing the beta-ketoester pendant group are also candidates for further reactions with compounds such as hydroxylamine or hydrazines to give mixed heterocyclic compounds. The products, BIDs, or their derivatives [e.g., BIDsisoxazolinones] are also good candidates for biol. testing in agriculture and medicine. Grant Support: National Science Foundation's--Research at Undergraduate Institutions through grants CHE # 0212699, the United States Department of Agriculture, NRICGP # 2002-35504-12853