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Reactions of Substituted (Methylthio)benzylidene Meldrum's Acids with Secondary Alicyclic Amines in Aqueous DMSO. Evidence for Rate-Limiting Proton Transfer

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journal contribution
posted on 24.12.2004, 00:00 by Claude F. Bernasconi, Mahammad Ali, Kelly Nguyen, Viola Ruddat, Zvi Rappoport
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 ; the second step involves deprotonation of to form ; while the third step represents general acid-catalyzed conversion of 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 or rate-limiting conversion of to products. A detailed structure−reactivity analysis indicates that for the reactions with piperazine, 1-(2-hydroxyethyl)piperazine, and morpholine it is deprotonation of that is rate limiting, while for the reaction with piperidine, conversion of to products is rate limiting.