Additivity of Substituent Effects

A useful equation which allows one to calculate the chemical shifts of aliphatic carbon atoms is 

To calculate the chemical shift of carbon (i), we proceed as follows  

1 increment for one a-C02H from Table 4.5 28.3 increment for one a-NH group from Table 4.5 2.0 increment for one jS-COO group from Table 4.5 0.3 increment for one 5-carbon front Table 4.5 

Number of non-hydrogen substituents on the most branched a-carbon (valid only for those substituents marked with an asterisk) 

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The steric requirements of the enhanced interaction between arylsulfinyl or arylsulfonyl groups and the benzene ring in bis(4-hydroxyphenyl)sulfoxides or sulfones were examined by Oae and colleagues through the introduction of methyl groups in two or four of the positions ortho to SO or S02. As in the work described earlier for S02Me, effective values for the combined influence of the substituents o (obs.) were determined and compared with o (calc.) computed on the basis of strict additivity of substituent effects on the dissociation... 

The additivity of substituent effects, demonstrated by (16), was the first kinetic evidence for a symmetrical charge distribution in the rate-limiting transition states of alkene bromination. 

Other papers in the series Chemometrical Analysis of Substituent Effects are on additivity of substituent effects in dissociation of 3,4-178 or 3,5-179disubstituted benzoic acids in organic solvents and on the ort/zo-effect180. In the last-mentioned, data for the dissociation of ortto-substituted benzoic acids in 23 solvents are combined with data on the reactions with DDM (Section IV.C) and with other rate and equilibrium data bearing on the behaviour of o/t/ o-substituents to form a matrix involving data for 69 processes and 29 substituents. 

The experimental result seems to support this model. Table 11 lists values for rotational barriers in some allyl radicals (Sustmann, 1986). It includes the rotational barrier in the isomeric 1-cyano-l-methoxyallyl radicals [32]/ [33] (Korth et al., 1984). In order to see whether the magnitude of the rotational barriers discloses a special captodative effect it is necessary to compare the monocaptor and donor-substituted radicals with disubstituted analogues. As is expected on the basis of the general influence of substituents on radical centres, both captor and donor substituents lower the rotational barrier, the captor substituent to a greater extent. Disubstitution by the same substituent, i.e. dicaptor- and didonor-substituted systems, do not even show additivity in the reduction of the rotational barrier. This phenomenon appears to be a general one and has led to the conclusion that additivity of substituent effects is already a manifestation of a special behaviour, viz., of a captodative effect. The barrier in the 1-cyano-l-methoxyallyl radicals [32]/... 

E. Additivity of Substituent Effects in Nuclear Magnetic Shieldi ... 

The atom-plus-ligand local-term approximation has been justified a posteriori for 30) and 57) shielding, since certain expected relationships of chemical shifts, such as additivity of substituent effects, were found to be absent for the observed shifts, but were fulfilled for i.e., after correction for the atom-plus-ligand diamagnetic term. Some examples are given in the following sections. 

The reported 2 e reductive cleavage of phenylsulphonylacetonitrile (PhSO CH CN) and the observation that in protic media the products were PhSO and CH CN, suggested that this reaction could be a useful source of CHjCN. However, careful re-examination showed that in acetonitrile solution the reaction is pseudo one-electron, analogous to the phosphonium and sulphonium salts (Scheme 8), and that phenylsulphonylacetonitrile is sufficiently acidic rapidly to protonate "CHjCN assuming additivity of substituent effects an estimate of pK 14-16 was made for PhSOjCHjCN, cf. pK 31 for CH,CN... 

Examination of nO chemical shifts of several 2-substituted and 2,5-disubstituted furans (85MRC985) has demonstrated the additivity of substituent effects by plotting the nO chemical shifts of 2,5-disubstituted furans versus those of the 2-substituted analogues. The electronic character of substituents alone does not determine l70 chemical shifts, because they do not correlate with Hammett constants. 

Another interesting set of results relating to additivity of substituent effects in heterocyclic systems is provided by the work of Katritzky and co-workers on electrophilic substitution in acidic media for... 

The difference in p values for equivalent reactions is probably not significant, particularly as there are often differences in reaction conditions and interpretations. Thus the kinetic form of some of the thiophene brominations are in doubt,258 there is a variation in acidic media used for the protodetritiation,260 and a different catalyst, SnCl4, is used for the thiophene acetylations 261,262 cf that for the benzenoid reaction, A1C13. In general, therefore, and in particular for the chlorination reaction,257 there appears to be a constant oi value for thiophene with additivity of substituents effects, but there is certainly room in this area for further experimentation and debate. 

DiLabio, G. A. Pratt, D. A. Wright, J. S. Theoretical calculation of ionization potentials for disubstituted benzenes additivity vs non-additivity of substituent effects./. Org. Chem. 2000, 65, 2195-2203. 

As a first reassuring statement, we can say that trends in chemical shifts of 13C are somewhat parallel to those of H, so that some of the feeling for H spectra may carry over to l3C spectra. Furthermore, the concept of additivity of substituent effects (see Sections 4.7.1 and 4.7.6) is useful for both spectra. The 13C shifts are related mainly to hybridization, substituent electronegativity, and diamagnetic anisotropy (to a lesser extent) solvent effects are important in both spectra. Chemical shifts for I3C are affected by... 

The data in Table 4 are not yet sufficient to give a final answer as to when additivity is to be expected and when not. They clearly show however that additivity of substituent effects definitely is not the exception. 

Polysubstituted radicals. In these cases no additivity of substituent effects is found. 

A fluorine substituent shortens the adjacent C—C bonds and lengthens the opposite bond in the cyclopropane ring. The lengthening of the C—C bond opposite to a CF2 group is remarkable (cf 98 and 104 in Table 9), but the mean C—C distance is smaller even in these molecules than in cyclopropane (1). In the other fluoro derivatives, all C—C bonds are shorter than in 1. The C—C bonds appear to be longer, the C—F bonds shorter in a cis isomer than in the trans isomer , and the same applies to C—C and C—F bonds in cis compared to trans CHF—CHF moieties within the same molecule. Ab initio calculations with a 4-2IG split valence basis set reflect the above trends quite well, except for the distinction of effects in the cis and trans forms ". The additivity of substituent effects, which... 

Tidwell and coworkers (Chwang etai, 1977 Koshy etai, 1979) focused their interest on the reactivity-structure relationship of the hydration rates. Additivity of substituent effects of the four substituents in the ethylene has been studied. As the interaction of substituents with the positive charge in the intermediate [36C "] is analogous to that in the electrophilic aromatic substitution intermediate, the substituent effects on the hydration of [36] may... 

The utility of rate correlations such as (22) depends on the additivity of substituent effects. Whereas the correlation of /3-substituents requires a different p value, this may be treated as total effects of three a-substituents in the developing intermediate [36C ], R, R and -CHR R. In practice a rather good correlation covers 22 orders of magnitude in reactivity without any clear evidence of curvature. Thus Tidwell stated (Koshy et al., 1979) that the Y-T correlation was unnecessary for the analysis of a large body of hydration data. 

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