title: Computer-Aided Reaction Design. Development of a New Facile Procedure to Synthesize 2-Mercapto-3-alkoxycarboxylate on the Basis of ab Initio Molecular Orbital Calculations.
abstract: This paper describes a new facial procedure to substitute a tosyloxy group in 2-(tosyloxy)alkanoate with SH(-) to yield 2-mercaptoalkanoate on the basis of ab initio MO calculations. Combination of substrate and solvent effects can control both reactivity and selectivity of reaction for 2-(tosyloxy)-3-alkoxycarboxylic acid which gave 2-mercapto-3-alkoxycarboxylic acid in good yield while its ethyl ester gave alpha,beta-unsaturated carboxylate ester as a main product. The difference of carboxylate moiety in the substrate causes remarkable change in reactivity and selectivity. To clarify origin of the difference, ab initio MO calculations in the gas phase and in DMF have been carried out. The solvent effect was considered at RHF/6-31+G with the IPCM-SCRF model. It was confirmed that the substrate with an ester fragment prefers the E1cB to the S(N)2 mechanism. In the transition state of the S(N)2 mechanism with a carboxylate ion fragment, the nucleophile SH(-) locates far from the reaction center due to the electrostatic repulsion between the COO(-) fragment and SH(-). This repulsion causes high activation barrier in the gas phase while polar solvent can reduce the barrier height. Therefore, reaction conditions can control reactivity of carboxylic acid. On the basis of analysis of the MO calculations, subsequent experiments were designed for a new dianion system to synthesize 2-pyrimidinylthio carboxylic acid from 2-tosyloxy carboxylate. We succeeded in developing a new facile method that the two reactions for thioether carried out in a one-pot procedure in excellent yield.
authors.affiliation: Department of Chemistry and Chemical Engineering, Faculty of Engineering, Yamaguchi University, Tokiwadai, Ube 755, Japan and Agrochemical Research Department, Ube Laboratory, Ube Industries, Ltd.1978-5 Kogushi, Ube 755, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Fukuda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Akiyoshi
authors.forename: Kenzi
authors.initials: K
authors.lastname: Hori