Reactions of substituted (methylthio)benzylidene Meldrum's acids with secondary alicyclic amines in aqueous DMSO. Evidence for rate-limiting proton transfer.
The replacement of the methylthio group of substituted methylthiobenzylidene Meldrum's acids (2-SMe-Z) by secondary alicyclic amines occurs by a three-step mechanism. The first step is a nucleophilic attachment of the amine to 2-SMe-Z to form a zwitterionic intermediate T(+/-)(A); the second step involves deprotonation of T(+/-)(A) to form T(-)(A); while the third step represents general acid-catalyzed conversion of T(-)(A) to products. At high amine and/or high KOH concentration nucleophilic attachment is rate limiting. At low amine and low KOH concentration the reaction follows a rate law that is characteristic for general base catalysis which, in principle, is consistent with either rate-limiting deprotonation of T(+/-)(A) or rate-limiting conversion of T(-)(A) to products. A detailed structure-reactivity analysis indicates that for the reactions with piperazine, 1-(2-hydroxyethyl)piperazine, and morpholine it is deprotonation of T(+/-)(A) that is rate limiting, while for the reaction with piperidine, conversion of T(-)(A) to products is rate limiting.
Bernasconi
Claude F
CF
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA. bernasconi@chemistry.ucsc.edu
Ali
Mahammad
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Nguyen
Kelly
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Ruddat
Viola
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Rappoport
Zvi
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