Hammett equation—continued

A completely different approach has been taken by Hine, who has considered that the substituent and reaction center are not really distinct, both being substituents in a benzene nucleus, and has then related substituent and reaction constants. Although of considerable theoretical interest, Hine s work has little bearing on practical applications of the Hammett equation since he starts from the premise of unique, single-valued substituent constants. This premise is invalid whether we are utilizing the naive approach with three separate, well-defined sets or the more refined methods with a continuous range of para values. 

Some radicals (e.g., tert-butyl, benzyl, and cyclopropyl), are nucleophilic (they tend to abstract electron-poor hydrogen atoms). The phenyl radical appears to have a very small degree of nucleophilic character. " For longer chains, the field effect continues, and the P position is also deactivated to attack by halogen, though much less so than the a position. We have already mentioned (p. 896) that abstraction of an a hydrogen atom from ring-substituted toluenes can be correlated by the Hammett equation. 

Molecular Similarity and QSAR. - In a first contribution on the design of a practical, fast and reliable molecular similarity index Popelier107 proposed a measure operating in an abstract space spanned by properties evaluated at BCPs, called BCP space. Molecules are believed to be represented compactly and reliably in BCP space, as this space extracts the relevant information from the molecular ab initio wave functions. Typical problems of continuous quantum similarity measures are hereby avoided. The practical use of this novel method is adequately illustrated via the Hammett equation for para- and me/a-substituted benzoic acids. On the basis of the author s definition of distances between molecules in BCP space, the experimental sequence of acidities determined by the well-known a constant of a set of substituted congeners is reproduced. Moreover, the approach points out where the common reactive centre of the molecules is. The generality and feasibility of this method will enable predictions in medically related Quantitative Structure Activity Relationships (QSAR). This contribution combines the historically disparate fields of molecular similarity and QSAR. 

The need for substituent constants of groups for which experimentally determined values are unavailable continually recurs. To supply this need methods of estimation of substituent constants are required. The first successful attempt to estimate substituent constants is due to Charton (50). The basis of this method is that a data set with substituents of the type ZW, where Z is variable and W is constant, can be treated in two equivalent ways. The system has the form ZWGY. The substituent can be taken to be Z, and the skeletal group to be WG or, the substituent can be assumed to be ZW, and the skeletal group to be G. In that case, let the composite substituent constant, ot,zw represent the effect of the ZW group, and the composite substituent constant, Hammett equation, some quantity Q which is to be correlated is given by. 

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