Transmission of Substituent Effects through Heterocyclic Systems

Transmission of Substituent Effects through Heterocyclic Systems A. Six-Membered Ring Systems 

The problems encountered in any attempt to treat the transmission of the effects of one substituent in a disubstituted heterocycle through the heterocyclic nucleus to a reaction site in the other substituent (i.e. the side-chain) are enormous, and it is consequently not surprising that relatively little work has been done in this area. First, while in benzene derivatives there are three positions, i.e. three relations between substituent and reacting side-chain to be considered, the number of complexities is much greater in heterocycles. Thus, e.g., in pyridine alone, after elimination of the orientations involving a vicinal relationship between substituent R and the side-chain Y to which no Hammett-type relation is likely to be applicable, the following cases should be considered  

In the cases 6-R-3-Y and 5-R-2-Y, the relation of R to Y corresponds to the para relation in benzene. When Y is in the 4-position, only meta-type (2-R or 6-R) substituents are possible. With R in the 2-position, aside from the one para-type relation (5-R-2-Y), two different metatype relations (4-R- and 6-R-2-Y) are possible, and the reactivity need not be the same for these two. Two ways suggest themselves to overcome this difficulty One might attempt to define separate a-values for substituents, depending not only on the relative position with respect to the side-chain, as in and Op, but also in relation to the heteroatom  

Throughout, R will be used to designate the rate (or equilibrium) affecting substituent, Y the reacting side-chain. 

The alternate procedure, which has actually been applied, is to define separate reaction constants p, pp, and py), depending on the location of the side-chain relative to the heteroatom, and to make separate correlations. Here, the remaining uncertainty is that for 2-Y there are the two meta-type positions mentioned above. This is the approach which has been used successfully in the few reported correlations to be discussed below. 

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