The preparation of 3-substituted 1,2-benzisothiazole-1,1-dioxides from the condensation-cyclization of dilithiated β-ketoesters with methyl 2-(aminosulfonyl)benzoate or 1,2-benzisothiazol-3(2H)-one-1,1-dioxide

Abstract

Several β‐ketoesters were dilithiated with an excess of lithium diisopropylamide, followed by condensation with methyl 2‐(aminosulfonyl)benzoate to give intermediates that were not isolated but cyclized to 3‐substituted 1,2‐benzisothiazole‐1,1‐dioxides. In most instances involving the ester‐sulfonamide, a single β‐ketoester tautomer is usually formed after recrystallization from ethanol. The same dilithiated β‐ketoesters generally condense less well with 1,2‐benzisothiazol‐3(2H)‐one‐1,1‐dioxide (saccharin) under the same conditions to afford the same products usually in the same or lower yields. The use of N,N,N',N'‐tetramethylethylenediamine during these syntheses has sometimes resulted in improved yields of products.

Preparation of spiro[benzoisothiazole‐isoxazole] dioxides from dilithiated c(α),O‐oximes and methyl 2‐(aminosulfonyl)benzoate

“…Recrystallized products 6 and 9-12 contained solvent molecules. We have previously obtained products containing solvents included in the crystal, but not to the extent found in this study [16,18,21,22]. We also obtained liquid chromatographs with mass spectral detection (LCMS) for each product.…”

“…There is one account involving this complex and dilithiated -ketoesters that is favorable, especially with regard to yield of products [20]. One of our initial projects involving the same type of dilithiated -ketoester intermediates and ester-sulfonamide 3 usually improved the products yield or permitted the reaction to occur [16].…”

“…The utilization of the latter ester-sulfonamide 3 led to preparations of 3-benzoisothiazole dioxide--ketoesters [16] and benzoisothiazoloisoquinolinone dioxides, the latter being a new four fused ring heterocyclic system [17]. The ester-sulfonamide 3 has also been used in the preparation of pyrazolyl-o-benzenesulfonamides 4 [18] by the condensation of ester-sulfonamide 3 with dilithiated phenylhydrazone 2, followed by acid cyclization of C-acylated intermediates to 4 instead of spiro(BID-pyrazole) 5.…”