The susceptibility of coumarins to alkaline hydrolysis, resulting in the formation of cis-coumarinate (and subsequently trans-coumarinate) polyanions is well known (Decker and Becker, 1922;Garrett et al., 1971; Mattoo, 1957; Bowden et al., 19611;Lippold and Garrett, 1971). For the most part, studies of substituent effects on the rates of alkaline hydrolysis of coumarins have been limited to derivatives with relatively weakly interacting functional groups. However, the coumarins of greatest economic interest are hydroxylated derivatives some of which are used as anticoagulants, fluorescent probes and optical components of mode-locked lasers (Shank et al., 1970; Trozzolo et al., 1974;Schulman and Rosenberg, 1979). The resistances of these substances to decomposition (Connors et al., 1979) under various solution conditions is therefore, of more than academic interest.The ionization of the hydroxy group which ought to play a dramatic role in the relative Iabilities of variously substituted hydroxycoumarins to attack by OH-, introduces an excellent opportunity to assess the relative importances of strong conjugative and electrostatic influences on the hydrolysis of coumarins.In the present note we consider the influence of the position of the hydroxy group on the second-order 'rate constants for the hydrolysis of 3-, 4-and 7-hydroxycoumarin and some related anticoagulants-warfarin, acenocoumarol and phenprocoumonthe drugs of choice in the U.S.A., The Netherlands and the Federal Republic of Germany, respectively. Because the hydroxy groups of all the compounds studied are fully ionized at the pH where the hydrolyses were studied * To whom correspondence should be addressed. ' The value of pK, -7.12fO.05 at 22OC was recently reported for the 3-isomer (Wolfbeis, 1981).0378-5173/82/0000-0000/82.75 D

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