Hydrolysis of amides: a kinetic study of substituent effects on the dilute acid hydrolysis of N-substituted acetamides

A kinetic study has oeen made of the dilute acid hydrolysis of eight N-alkyl substituted acetamides. Rate constants have been determined for these amides over a temperature range of 65° to 95° and from these results values of the free energies, enthalpies and entropies of activation for the reaction have been calculated. Changes in the rate constants are showi to be governed by the steric effects of the substituents, An analysis of the results in terms of various appropriate free energy relationships has been made. It was found that, while the normal Taft steric parameters, Es are not directly applicable to these systems because they are defined for systems involving changes in the acyl portion of esters, they can be used in conjunction with a parameter A6 which makes allowance for the change in 'six-number' which a substituent experiences when it is moved from the acyl to the alkyl portion of the molecule. The inevitable large errors in ΔH* and ΔS* were found to obscure any meaningful study of structural relationships in these quantities.