Substituent Constants for Heteroatoms

The concept that replacement of a CH group in benzene by a heteroatom can be treated as a substitution in the sense of the 

Willi and W. Meier, Helv. Chim. Acta 39, 54 (1956) cf. A. V. Willi, ihid. 

The total experimental material known to the present authors is summarized in Table I. Unfortunately, few of the data presented come from the most thoroughly studied and best documented reaction series. However, the picture is quite discouraging. Very likely, separate a - and normal ct-values and, possibly further, a separate CT+-value might be applicable for the 2- and 4-aza groupings since resonance structures such as 2-4 may contribute in appropriate systems, although 4 may not be too important, and, consequently. 

CT+-values may not differ too widely from ct-values. Since the charges in 2 and 4 actually reside in the ring, the pyridine system may, in addition, be particularly subject to the variability of cr-values, and consequently a careful analysis of some rather extensive material in the sense of some of the most refined methods might be very profitable 

It has also been suggested to treat various modified heterocyclic nitrogen atoms in the same manner. Thus, cr-values have been proposed for the protonated aza nitrogen, N+H, and for the N+0  

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This approach did not seem to be as satisfactory for those sulfamates having heteroatom substituents (hetero-sulfamates). Spillane suggested that the various electronic effects of the hetero-atoms probably introduce an additional variable that is apparently absent, or constant, for the carbosulfamates. Because molecular connectivity correlates structure with molecular volume and electronic effects, Spillane included molecular connectivity, (computed for the entire molecule, RNHSOO to the four variables, x, y, z, and V, and applied the statistical technique of linear-discrimination analysis to 33 heterosulfamates (10 sweet, 23 not sweet). A correlation of >80% was obtained for the x, z, x subset 5 of the 33... 

In this equation the substituent constant refers specifically to the substituent attached to the heterocyclic ring and its value depends not only on the nature of the substituent, but also on its position with respect to both the reducible group and the heteroatom. It will also depend upon the type of heterocyclic system. The reaction constant Pn, het.R describes the ease of reduction of the substituent R and will vary with the type of heterocyclic system and the position of the substituent R with respect to the heteroatom. Because of the limited number of known <7het-X values, it is more convenient to use a values derived from benzene systems and it has been shown that substituent effects across the 2,5-positions and CTmeta values for substituent effects across the 2,4-(3,5)positions.302 Using the equation... 

Interestingly, equation (10) does not hold for radical cations with the general structure 4-R-C6H4-X-CH3 where X is S, Se or Te.[14] In these species, the charge seems to be localized to the heteroatom which is reflected by the almost negligible effects of 4-substitution on the one-electron reduction potential (figure 2). The one-electron reduction potenticils of these radical cations is governed by the ionization potential of the heteroatom rather than by the substituent effects as described by the substituent constants. 

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