The effect of substituents on side-chain reactivity

Abstract

The Investigation is concerned with the effect of p-substituents on the rates and activation parameters in the ionisation (S(_N)1 reaction) of phenylmethyl halides. In these systems, substituents exert their effect on the rate almost entirely by altering the electron density at the reaction centre(^1). The work was designed to yield information about the effect of changing electron demand at the site of p-substitution in the transition state. The reaction of p-substituted benzyl halides with slightly moist formic acid was studied initially. In this system, the electron demand at the site of p-substitution can be expected to be large but the results were unsuitable for discussion of substituent effects in S(_N)l reactions since this mechanism did not operate throughout the series. Completely S(_N)l solvolysis appears to require the presence of an electron donating substituent and may not be attained by the p-methyl derivative. An extension to aqueous organic solvents showed that completely S(_N)l hydrolysis requires the presence of a p-phenoxy, or better electron releasing substituent. The hydrolysis of p-substituted p'-nitro-, p'-hydrogen-, and p'-raethoxy-benzhydryl chlorides undoubtedly occurs by the ionisation mechanism. The electron demand at the site of p-substitution was expected to decrease in the order, p'-nitro > p'-hydrogen > p'-methoxy and it is consistent with this view that the effect of any one p-substituent on the rate follows the same sequence. The kinetic effect of these p-substituents arises almost entirely from changes in the activation energy although the entropy of activation is significantly reduced by the introduction of p-phenoxy and p-methoxy substituents. In all three series, reaction is facilitated by electron releasing p-substituents, particularly by those which are polarisable with respect to electron demand at the reaction centre. There is, however, no simple relation between the magnitude of these polarisabllity effects and the electron demand at the site of p-substitution. As a result, simple free-energy relations of the Hammett type(^2) are inadequate in accounting for the effect of p-substituents on the rates, even in the present three similar series. The Tsuno-Yukawa equation(^3), which attempts to allow for polarisation and polarisabllity effects separately, describes the present rates more satisfactorily, if the reaction constants are derived from the results for the two p-substltuents with extreme polar properties. However, this equation assumes a linear relation for the response of substituents to a demand for electrons. It is concluded that the effects of p-substituents are more profitably discussed by using Ingold's approach(^4) of considering the polarisation and polarisability effects, and the reaction mechanism.