Substituent Effects on Reactivity

Regarding the substituent effect on reactivity of groups in positions 4 and 5 there is little information in the literature. The reactivity of halogen in position 5 seems to be increased when an amino group is present in position 2. Substitution products are easily obtained using neutral nucleophiles such as thiourea, thiophenols, and mercaptans (52-59). 

Ipso substitution, in which the electrophile attacks a position already carrying a substituent, is relatively rare in electrophilic aromatic substitution and was not explicitly covered in Section 10.2 in the discussion of substituent effects on reactivity and selectivity Using qualitative MO cOTicepts, discuss the effect of the following types of substituents on the energy of the transition state for ipso substitution. 

Next we turn to the magnitudes of the p constants. Evidently if p = 0, there is no substituent effect on reactivity. Moreover because p = -I-1.000 by definition for the aqueous ionization of benzoic acids, we have a scale calibration of sorts. Wiberg gives examples of p as a measure of the extent of charge development in the transition state. McLennan" has pointed out that p values must first be adjusted for the transmission factor before they can be taken as measures of charge devel-... 

The effect of substituents on reactivity may be understood in terms of Fig. 31. The ground state profile (unbroken bold line) is the result of the mixing of DA, D+A- and 3D 3A configurations (107). Substituent effects on reactivity appear to be dominated by their effect on D+A. Substituents that stabilize D+A lower its energy along the entire reaction co-ordinate (broken line) and lead to a lower energy reaction profile (broken bold line). 

By comparison with the extensive kinetic results available for the quatemization of six-membered rings, especially where substituent effects on reactivity are concerned, few quantitative studies have involved five-membered heterocyclic rings. These are considered next. 

D. Substituent Effects on Reactivity and the Electronic Structure of the Transition State... 

Sn2 Reactions Kinetic and Stereochemical Analysis—Substituent Effects on Reactivity... 

Substituent Effects on Reactivity and Regioselectivity of Ar-SE Reactions of Monosubstituted Benzenes... 

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