Multiple Substituent Effects

Using a multiple linear regression computer program, a set of substituent parameters was calculated for a number of the most commonly occurring groups. The calculated substituent effects allow a prediction of the chemical shifts of the exterior and central carbon atoms of the allene with standard deviations of l.Sand 2.3 ppm, respectively Although most compounds were measured as neat liquids, for a number of compounds duplicatel measurements were obtained in various solvents. 

Singh et al [54] used a 13C NMR spectrometric method and reported the chemical shifts of primaquine and chloroquine. The signals are assigned on the basis of substituent effects on benzene shifts, intensities, multiplicities in single-frequency off-resonance decoupled and the comparison with structurally related compounds. 

Finally, as shown in Table 13, p for an aromatic ring is also strongly dependent on the other substituents at the double bond it varies from —1.6 to — 5.5 on going from a-methoxystyrenes to stilbenes. This variation, which is related to the well-known non-additivity of multiple substituent effects, and contrasts with what is observed for alkene bromination, is discussed in the next paragraph, devoted to substituent interaction and selectivity relationships in bromination. 

The treatment of non-additivity has also been applied to a large variety of multiple substituent effects on various reactions (Argile et al., 1984) and, in particular, to the bromination of X,Y-disubstituted benzenes where two substituents on the same ring interact strongly (Dubois et al, 1972b) the interaction constant q = — 7.98, associated with a very negative p-value, —12.05, is much higher than those found for the bromination of arylolefins. 

Table 15 Non-additivity of multiple substituent effects p-dependence on X for a substituent Y and interaction constants in arylolefin bromination in methanol at 25°C.

Equations (37)—(39), where the non-additivity of multiple substituent effects is described by a cross-term, express correctly the rate data for bromination and other reactions of polysubstituted substrates. The question arises, therefore has the interaction constant, q, any physicochemical meaning in terms of mechanism and transition state charge To reply to this question, selectivity relationships (42) that relate the p-variation to the reactivity change and not to any substituent constant, have been considered (Ruasse et al., 1984). 

Aryl substitution on germanium, whether single or multiple, has only a small effect on the rate constants for hydrogen atom transfer, whereas the rate constant increases substantially with substitution of an alkyl group on Ge by a silyl group, much as observed with the silanes. A strong substituent effect also was observed for germane 19. 

Fuchs, R. Carlton, D. M. Multiple substituent effects in the solvolysis and thiosulfate reactions of 4-substituted a-chloro-3-nitrotoluenes. /. Org. Chem. 1962, 27,1520-1523. 

Vecera, 1973) none of these systems involves a sufficient number of substituents for our purpose. The necessary additional data have now been supplied (Fujio et al, unpublished). Schade and Mayr (1988) later demonstrated that various sets of solvolysis rates, determined under different conditions, especially in different solvents, are linearly correlated with each other, and by using these linear correlations, the solvolytic data obtained under different conditions were converted into a standard set in ethanol at 25°C this data set does not appear to be more extensive than ours as regards variety of substituents, but it provides evidence for the linearity between multiple substituent effects in ethanolysis and those in any other solvolyses, especially in the standard set in 85% aqueous acetone at 0°C. 

By similar treatments, the effects of many substituents and combinations of substituents were evaluated, and found to give a reasonably linear correlation with reaction rates when plotted by the Hammett-Taft method. The value of —3.3, determined graphically, is close to the value of — 3.49 reported for solvolysis of substituted cyclohexyl tosylates. Although the general validity of the multiple-path treatment has still to be demonstrated, it may be noted that similar calculations, using an attenuation factor of 0.51, produced a reasonable correlation of substituent effects at C(3> and C(i7) with rates of bromine addition to the 5,6-ethylenic bond [17]. 

Scheme 37. The symmetry criterion for cation radical formation via outer sphere electron transfer. Substituent effects in mono- and disubstituted stilbenes are multiplicative log krei correlates with (t+ with p = -4.16 the oxidation potentials of these same stilbene derivatives correlate with the same substituent parameters with p = -5.02.

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