Extended selectivity relationship

The extended selectivity relationship for biphenyl. (From Stock, L.M. and Brown, H.C., in Advances in Physical Organic Chemistry, Vol. 1, Gold, V., Ed., Academic Press, London. With permission.)... 

The failure of the Selectivity Relationship and the Extended Selectivity Relationship presented a serious problem. The p-phenyl substituent activates the aromatic ring by the same mechanism as the p-methoxy group. Accordingly, it was suggested (Knowles et al., 1960) that the variation in reactivity was a reflection of the variability of resonance stabilization merely as a function of electron demand. The... 

An examination of the data for substitution in the 2-position of fluorene (Fig. 32) reveals a reasonable correlation. Some scatter is observed but no more than is generally encountered in an application of the Hammett treatment to data covering a wide range of reactivity. Certainly, there is no evidence for a pronounced curvature of the kind found in the related treatment of the data for biphenyl (Figs. 29 and 30). In contrast to substitution in the para position of biphenyl, substitution in the structurally equivalent 2-position of fluorene conforms to the Extended Selectivity Relationship (see, however, p. 147). 

The relative rates of substitution para to the chloro and bromo substituents agree with the predictions of the Extended Selectivity Relationship to about the same extent as the meta-halogens. The... 

Extended Selectivity Relationship. c Adopted Hammett a value. 

Fig. 2. The extended selectivity relationship for electrophilic reactions at the a position of thiophene. The numbers identify the reactions see Table XII.

Because systematic variations in selectivity with reactivity are commonly quite mild for reactions of carbocations with n-nucleophiles, and practically absent for 71-nucleophiles or hydride donors, many nucleophiles can be characterized by constant N and s values. These are valuable in correlating and predicting reactivities toward benzhydryl cations, a wide structural variety of other electrophiles and, to a good approximation, substrates reacting by an Sn2 mechanism. There are certainly failures in extending these relationships to too wide a variation of carbocation and nucleophile structures, but there is a sufficient framework of regular behavior for the influence of additional factors such as steric effects to be rationally examined as deviations from the norm. Thus comparisons between benzhydryl and trityl cations reveal quite different steric effects for reactions with hydroxylic solvents and alkenes, or even with different halide ions... 

This approach, with 8C as a substitute for p, is designated as the Selectivity Treatment. The alternative procedure for the examination of the substitution data, employing p as the principal reference parameter, is termed the Extended Selectivity Treatment. The Selectivity Treatment was first employed for the evaluation of linear relationships and c-g-constants. As more data have become available and an independent technique for the assessment of p has evolved, the Extended Selectivity Treatment has become more useful. 

The procedure adopted to portray the scope and utility of a linear free-energy relationship for aromatic substitution involves first a determination of the p-values for the reactions. These parameters are evaluated by plotting the values of log (k/ka) for a series of substituted benzenes against the values based on the solvolysis studies (Section IV, B). The resultant slope of the line is p, the reaction constant. The procedure is then reversed to assess the reliability and validity of the Extended Selectivity Treatment. In this approach the log ( K/ H) observations for a single substituent are plotted against p for a variety of reactions. This method assays the linear or non-linear response of each substituent to variations in the selectivity of the reagents and conditions. Unfortunately, insufficient data are available to allow the assignment of p for many reactions. It is more practical in these cases to adopt the Selectivity Factor S as a substitute for p and revert to the more empirical Selectivity Treatment for an examination of the behavior of the substituents. 

The reaction constants obtained in the previous section for numerous substitution reactions permit the examination of the applicability of a linear free-energy relationship by the Extended Selectivity Procedure. The utility of this approach is demonstrated by application to a series of data for side-chain reactions which are correlated with good precision by the Hammett equation. The variations as detected by the procedure serve as a convenient frame of reference for the behavior to be anticipated in other treatments. 

Figure 29 presents an analysis of the data for p-phenyl groups in the Extended Selectivity Treatment. The reactivity of the para position increases significantly with an increase in the electron demand of the substitution reaction. This result is confirmed by an analysis of the data through the Selectivity Relationship in which a linear relationship is predicted for a diagram of log pfh against S (Fig. 30). Again, curvature is evident. It must be concluded that the substitution reactions of biphenyl do not adhere to a linear free-energy relationship (Eabom and Taylor, 1961b Stock and Brown, 1962a).

The Selectivity Relationship was shown to be applicable for substitution in the meta and para positions of toluene (Section II). The fine adherence of the -methyl group to a linear free-energy relationship (Fig. 37) is apparently typical of the behavior of the other alkyl substituents, as illustrated for the p-ethyl, p-i-propyl, and p-t-butyl groups (Figs. 38-40). Indeed, the data for electrophilic substitution in toluene are better correlated by a linear relationship than are the data for ordinary side-chain reactions of p-tolyl derivatives (Stock and Brown, 1959a). In the Extended Selectivity Treatment (Fig. 25) the side-chain reactions show a slightly greater scatter from the correlation line than the aromatic substitution reactions. 

The application of the Extended Selectivity Treatment to the partial rate factors for the wi-fluoro, ra-chloro, and ra-bromo substituents is shown in Figs. 43-45. Too few data are available for ra-iodo. Inspection of these diagrams reveals that substitution meta to the halogens conforms to a linear relationship. No serious deviations are detected. The log mf values for non-catalytic chlorination are displaced from the correlation line, but this discrepancy is almost certainly the consequence of the failure of the additivity principle on which the results are based (Stock and Baker, 1962). 

The partial rate factors for many substituents in many substitution reactions have been explored in the previous sections. Analyses of these data by the Selectivity and Extended Selectivity Treatments indicate the adherence of the data to the predictions of a linear free-energy relationship, and only two groups, p-phenyl andp-fluoro, deviate significantly. Several comparisons of the applicability of a linear relationship for substitution and for Hammett side-chain reactions reveal the... 

In spite of these uncertainties, however, the utility of the reactivity-selectivity principle has been illustrated for a number of diverse areas of mechanistic interest. Such applications are being extended to other areas as well. For example, Olah has recently studied the mechanism of electrophilic addition to multiple bonds using selectivity data and concluded that the transition states of the bromine addition to alkenes are of a 7r-complex nature (Olah and Hockswender, 1974). Finally the large number of reactivity-selectivity relationships which have been discovered offer considerable experimental support for the various expressions and formulations of the Hammond postulate whose profound effect on modem mechanistic chemistry is now beyond question. 

Structure-reactivity relationship in polyarylcarbocation systems 334 Conformations of carbocations 334 Reactivity-conformation relationship 337 Stabilities of carbocations in the gas phase 343 Structural effects 343 Tlie resonance demand parameter 355 Theoretically optimized structures of carbocations 362 Reaction mechanisms and transition-state shifts 365 Extended selectivity-stability relationships 365 Ground-state electrophilic reactivity of carbocations 366 Sn2 reactions of 1-arylethyl and benzyl precursors 372 Concluding remarks 378 Acknowledgements 379 References 379... 

Fornal et al. [75] determined selectivity differences for bases in RP-HPLC under high pH conditions. They used quantitative structure retention relationships (QSRR) to model retention behavior. They reported that the stability of the columns they used (Waters XTerra MS, Zorbax Extend, Thermo BetaBasic) was limited with... 

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