Mechanisms of Nucleophilic Substitution

Nucleophilic substitutions at sp3-hybridized carbon are among the most useful syn- 

Side Reactions in Organic Synthesis. Florencio Zaragoza Dorwald Copyright 2005 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-31021-5 

Compared with SnI or Sn2 reactions, relatively few examples of radical nucleophilic substitutions have been reported [6-8,16, 22-25]. This suggests that the structural requirements of nucleophile and electrophile for such processes are more stringent than for non-radical nucleophilic substitutions. In the following sections the focus will be on the more generally applicable non-radical SnI and Sn2 reactions. 

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Comparison of SnI and Sn2 Mechanisms of Nucleophilic Substitution in Alkyl Halides... 

Because carbocations are key intermediates in many nucleophilic substitution reactions, it is important to develop a grasp of their structural properties and the effect substituents have on stability. The critical step in the ionization mechanism of nucleophilic substitution is the generation of the tricoordinate carbocation intermediate. For this mechanism to operate, it is essential that this species not be prohibitively high in energy. Carbocations are inherently high-energy species. The ionization of r-butyl chloride is endothermic by 153kcal/mol in the gas phase. ... 

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

Studies of the solvolysis of 1-phenylethyl chloride and its p-substituted derivatives in aqueous trifluorethanol containing azide anion as a potential nucleophile provide details relative to the mechanism of nucleophilic substitution in this system. 

The role of nitronium ion in the nitration of benzene was demonstrated by Sir Christopher Ingold—the same person who suggested the n1 and n2 mechanisms of nucleophilic substitution and who collaborated with Cahn and Prelog on the R and S notational system. 

Ionization is obviously important in the SnI mechanism of nucleophilic substitution, and indeed two ion pair intermediates have been invoked.These are related as in Eq. (8-19), where (s) represents the solvent. 

Additive Mechanism of Nucleophilic Substitution at Multiple-Bonded... 

For a review of mechanisms of nucleophilic substitutions at di-, tri-, and tetracoordinated sulfur atoms, see Ciuffarin, E. Fava, A. Prog. Phys. Org. Chem., 1968, 6, 81. 

This intermediate is similar to those encountered in the neighboring-group mechanism of nucleophilic substitution (see p. 404). The attack of W on an intermediate like 2 is an Sn2 step. Whether the intermediate is 1 or 2, the mechanism is called AdE2 (electrophilic addition, bimolecular). 

Reactivity factors in additions to carbon-hetero multiple bonds are similar to those for the tetrahedral mechanism of nucleophilic substitution. If A and/or B are electron-donating groups, rates are decreased. Electron-attracting substituents increase rates. This means that aldehydes are more reactive than ketones. Aryl groups are somewhat deactivating compared to alkyl, because of resonance that stabilizes the substrate molecule but is lost on going to the intermediate ... 

The mechanism of nucleophilic substitution in primary halogenoalkanes proceeds as follows, using 1-bromobutane as an example ... 

Figure 3.14 Mechanism of nucleophilic substitution reactions of lignin during sulfite pulping.

Mechanisms of Nucleophilic Substitutions Under Phase Transfer Conditions... 

Organic chemistry and instrumental analysis Synthesis 3 Mechanisms of nucleophilic substitution reactions... 

Going over the basics and mechanisms of nucleophilic substitution reactions Mastering mechanisms of elimination/addition reactions Determining synthesis strategies for aromatic systems... 

The electrophile shown in step 2 is the proton. In almost all the reactions considered in this chapter the electrophilic attacking atom is either hydrogen or carbon. It may be noted that step 1 is exactly the same as step 1 of the tetrahedral mechanism of nucleophilic substitution at a carbonyl carbon (p. 331), and it might be expected that substitution would compete with addition. However, this is seldom the case. When A and B are H, R, or Ar, the substrate is an aldehyde or ketone and these almost never undergo substitution, owing to the extremely poor nature of H, R, and Ar as leaving groups. For carboxylic acids and their... 

In this case participation by R assists in removal of X in the same way that neighboring groups do (p. 309). Indeed, Rita neighboring group here. The only difference is that, in the case of the neighboring-group mechanism of nucleophilic substitution, R never becomes detached from A, while in a rearrangement the bond between R and A is broken. In either... 

Stereochemical evidence for the mechanism of nucleophilic substitution at a tetracovalent phosphorus atom has been mainly forthcoming from the experiments of Michalski et a/.48-50 with esters containing thiophosphoryl centers. Until recently, the inaccessibility of suitable optically active phosphorus compounds precluded stereochemical investigations on the mechanisms of their hydrolysis. 

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