The catalytic effect of metal ions on the hydrolysis of ethyl-S-phosphate (1a), cysteamine-S-phosphate (1b), and 2-carboxyethyl-S-phosphate (1c) has been investigated. Fe(III) and Al(III) markedly inhibit the rate of hydrolysis of all three thiolphosphates, decreasing kabs by ca. 102 at pH 3; Zn(II) and Mn(II) are almost without effect on the hydrolysis rates of 1b and 1c; and Cu(II) in less than substrate concentration increases kabs by 102 for 1b and 1c but has no effect on 1a. The requirement of a suitably located ligand for catalysis is obvious. The mechanism of the Cu(II)-catalyzed hydrolysis of 1b has been examined in detail and includes the following pertinent characteristics: (1) rate-determining formation of two hydrolytically labile complexes from monoanion (NH2RSPO3H-) and/or dianion (NH2RSPO32-) and Cu(H2O)12+; (2) product inhibition by cysteamine because of the formation of a catalytically inactive cysteamine-Cu(II) complex; and (3) incursion of an oxidative Cu(II)-catalyzed conversion of cysteamine to cystamine at pH 7, which relieves product inhibition. The synthetic phosphorylating potential of this reaction in acetonitrile-alcohol solvent mixtures indicates its utility in the synthesis of simple phosphate monoesters. A rationale for the effectiveness of Cu(II) catalysis in these systems is offered.
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