Substituent interaction energies

The energy data for di- and polysubstituted benzenes have been analyzed in terms of substituent interaction energies. These are given by energies of reactions of the type shown by Equation 1 ... 

The possibility of an entropy-enthalpy relationship for the reaction was examined and found to give a correlation coefficient of only 0.727 which was however improved to 0.971 if only the external contributions to these parameters were used, i.e. these contributions arising from solvent interactions only. If compounds with substituents ortho to the amino group were excluded, this further improved to 0.996 and is likely therefore to be real [cf. the comments on p. 9). It was argued that the different amounts of desolvation of the aromatic on going to the transition state would depend upon the substituent, and that the resultant greater freedom for solvent molecules would mean decreased interaction energy or increased enthalpy so that the linear relationship follows. 

An estimate of the energy of steric repulsion may be obtained by comparing the observed heat of polymerization with the value calculated on the assumption that the interaction energy between substituents is zero. For the latter purpose, we consider the following steps... 

Insertion of the monomer in the Zr-CH2C H5 bond in (VIII) will therefore require additional energy, equal to the interaction energy of the phenyl group with the metal atom. Since transition metal benzyl compounds are stabilized by the interaction of the aromatic nucleus with the metal atom. This explanation predicts that benzyl compounds with substituents on the a-carbon atom will be unstable. Attempts have been made H6) to... 

Retention volumes of monosubstituted benzenes, benzoic acid, phenols, and anilines have been measured in RPLC [76]. Buffered acetonitrile/water and tetrahydrofuran/water eluents were used with an octadecylsilica adsorbent. From the net retention volumes, a substituent interaction effect was calculated and described with the linear free energy relationship developed by Taft. The data was interpreted in terms of hydrogen bonding between the solutes and the eluent. 

FIGURE 6. Schematic plot of LUMO energies of aromatic compounds and the resulting LUMO from the interaction of the aromatic LUMO and the substituent LUMO37. Energy for the N02 substitutent LUMO is approximated by the EA of nitromethane37. Reprinted with permission from Reference 37. Copyright (1989) American Chemical Society... 

Recently, Huisgen and coworkers have reported on the first unequivocal example of a nonconcerted 1,3-dipolar cycloaddition.27 Sustmann s FMO model of concerted cycloadditions envisions two cases in which the stepwise mechanism might compete with the concerted one.21 Two similar HOMO-LUMO interaction energies correspond to a minimum of rate and a diradical mechanism is possible, especially if stabilizing substituents are present. A second case is when the HOMO (l,3-dipole)-LUMO (dipolarophile) is strongly dominant in the transition state. The higher the difference in rr-MO energies of reac-... 

Some studies have shown that a correlation between aqueous solubility and hydrophilicity of the promoiety may not always exist. For example, the incorporation of polar, hydrogen-bonding substituents in a series of prostaglandin derivatives resulted in an increase in both crystalline interaction energies and hydration energies, and therefore aqueous solubility did not increase (Anderson and Conradi, 1980). Predicting an increase in water solubility as a result of an increase in the hydrophilicity of a promoiety is considered unreliable (Anderson and Conradi, 1987). 

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