Substituent effects nucleophiles

As is broadly true for aromatic compounds, the a- or benzylic position of alkyl substituents exhibits special reactivity. This includes susceptibility to radical reactions, because of the. stabilization provided the radical intermediates. In indole derivatives, the reactivity of a-substituents towards nucleophilic substitution is greatly enhanced by participation of the indole nitrogen. This effect is strongest at C3, but is also present at C2 and to some extent in the carbocyclic ring. The effect is enhanced by N-deprotonation. 

The nucleophilic reactivity of 2-halogenothiazoles is strongly affected by the substituent effect, depending on the kind of substitution reaction. Positions 4 and 5 can be considered as meta and para , respectively, with regard to carbon 2 and to groups linked to it consequently, it is possible to correlate the reactivity data with Hammett s relationships. 

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). 

A nitro group behaves the same way m both reactions it attracts electrons Reaction is retarded when electrons flow from the aromatic ring to the attacking species (electrophilic aromatic substitution) Reaction is facilitated when electrons flow from the attacking species to the aromatic ring (nucleophilic aromatic substitution) By being aware of the connection between reactivity and substituent effects you will sharpen your appreciation of how chemical reactions occur... 

In addition to steric effects, there are other important substituent effects which determine both the rate and mechanism of nucleophilic substitution reactions. It was... 

In spite of the potential complexity of the general problem, even when restricted to the reagent family of amines, the nucleophilicities of such series as meta- and pom-substituted pyridines and anilines appear to correlate very closely with the expected substituent effects and with the basicities. This has been verified in the following cases (i) The reaction of pyridines (R = H, m- andp-CHs) with 2-chloro-3-nitro-, 2-chloro-5-nitro-, and 4-chloro-3-nitro-pyridines. ... 

In agreement with the assumption of a nucleophilic bimolecular reaction, increased electron deficiency at the site of the displacement causes acceleration and vice versa. The reaction is very sensitive to substituent effects, in accordance with what is found with nitrobenzene derivatives and what is generally expected for a nuclear... 

W-OCH3 group should lower the basicity of naphthoic acids (both a and j8) and the nucleophilic reactivity of aza-benzene derivatives. In terms of a, the substituent effect for alkoxy groups wiU be negative at all positions. The w-SCHg group behaves similarly. 

A nucleophile can interact reversibly with an electron-attracting substituent (e.g., —CN or —CHO) in the course of nucleophilic displacement of another group (e.g., halo), thereby producing a spurious substituent effect (cf. 96). The interaction has been found to vary with the nucleophile (see Section II, E). 

Zahler and elaborated in a series of papers by Miller and co-workers and in Bunnett s publications, many of which are cited in Section I, D. It should be pointed out that the effects of substituents on nucleophilic substitutions show important differences from their effects on other reactions or on equilibria which involve competition for a lone-pair of electrons on another group or stabilization of negative charge on some atom of the reacting moiety. The cr-constants for nucleophilic substitutions differ from those determined in the latter work in that they show the response of the substituent to a strong demand for stabilization of negative charge on the substituent itself, especially by resonance. 

The selective reaction of anionic 3,6-dichloro-4-sulfanilamidopy-ridazine with excess methanolic methoxide at the 3-position is another indication of the absence of major steric effects in most nucleophilic substitutions, as a result of the direction of nucleophilic attack (cf. Section II, A, 1). The selectivity at the 3-position is an example of the interaction of substituent effects. The sulfonamide anion deactivates both the 3-chloro (ortho direct deactivation) and... 

The effect of the leaving group and of other substituents on nucleophilic substitution of cinnolines is discussed in Sections II, D and II, E, respectively. 

The effect of nuclear substituents on nucleophilic substitution of quinoxalines is included in Section II, E, and in section III, A,... 

The results are consistent with either an ANDN-like mechanism, i.e., a concerted attack of the nucleophile with the release of N2, or a two-step AN + DN mechanism. On the other hand, substituent effects, as found by Crossley and coworkers (1940) and later verified by Schulte-Frohlinde and Blume (1968 b), cannot be understood on the basis of such bimolecular mechanisms. Instead of an accelera-... 

However, measurements of substituent effects supported the hypothesis that the aryl cation is a key intermediate in dediazoniations, provided that they were interpreted in an appropriate way (Zollinger, 1973a Ehrenson et al., 1973 Swain et al., 1975 a). We will first consider the activation energy and then discuss the influence of substituents, as well as additional data concerning the aryl cation as a metastable intermediate (kinetic isotope effects, influence of water acitivity in hydroxy-de-di-azoniations). Finally, the cases of dediazoniation in which the rate of reaction is first-order with regard to the concentration of the nucleophile will be critically evaluated. 

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