Entropy Changes and Reactivity

The role of entropy in determining the order of reactivity within a reaction series has been demonstrated for several other reaction systems. A classic example of a reaction in which relative rates are largely determined by TAS terms is semicarbazone formation in phosphate buffers (Price and Hammett, 1941). The differential thermodynamic parameters of activation, with acetone taken as the standard reactant, are given in Table 14. The ninety-fold decrease in reaction 

Relative Entropies and Energies of Activation for Semicarbazone Formation at 12.5° 

The rule of Price and Hammett has been found to hold in several other kinetic studies. However, it has been shown to fail in oxime formation under conditions identical with those of the semicarbazone study (Fitzpatrick and Gettler, 1956). This is perhaps not surprising in view of the known complexity of semicarbazone and oxime formation, but it should serve as a warning that the effect of structure on entropy is by no means well understood. 

Because of the complex nature of semicarbazone formation, it is difficult to say with certainty at what stage in the reaction the entropy variations originate. Recent work on the mechanism of the reaction bears on this point. Jencks and Carriuolo (1960) have shown that above pH 4 the reaction involves a fast preequilibrium between carbonyl and semicarbazide, followed by a rate-controlling, acid-catalyzed dehydration of the addition compound. 

Price and Hammett s rule has found confirmation in the reaction of benzaldehyde with acetone and ethyl methyl ketone (Gettler and Hammett, 1943), in the acid-catalyzed hydration of olefins (Taft, 1956a), in the hydrolysis of esters catalyzed by ion-exchange resins (Samelson and Hammett, 1956), in acid-catalyzed deoxymercuration (Kreevoy et al., 1962), and in the esterification of carboxylic acids in methanol (Smith, 1939). Taft (1956b) has noted that the rule seems to require the following modifications. The entropy-bearing substituent 

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