Nucleophilic substitution neighboring group effect

In a few reactions, nucleophilic substitution proceeds with retention of configuration, even where there is no possibility of a neighboring-group effect. In the SNi mechanism (substitution nucleophilic internal) part of the leaving group must be able to attack the substrate, detaching... 

On occasion, a molecule undergoing nucleophilic substitution may contain a nucleophilic group that participates in the reaction. This is known as the neighboring group effect and usually is revealed by retention of stereochemistry in the nucleophilic substitution reaction or by an increase in the rate of the reaction. 

The term intramolecular catalysis introduced by Bender is also widely used to describe neighboring group effects, especially when analogous intermolecular catalysis is observed. Thus this term is commonly used when referring to reactions that are subject to acid, base, and/or nucleophilic catalysis such as hydrolysis of esters, amides, and acetals the mutarotation of aldoses or the enolization of ketones. It is rarely used when referring to nucleophilic substitution reactions at saturated carbon. 

Since these methoxylated and acetoxylated sulfides have an acetal structure, it is expected that Lewis acid catalyzed demethoxylation should generate a carbocation intermediate which is stabilized by the neighboring sulfur atom. In fact, nucleophilic substitution with arenes has been successfully achieved as shown in Scheme 6.7 [43], This procedure is useful for the preparation of trifluoroethyl aromatics. As already mentioned, generation of carbocations bearing an a-trifluoromethyl group is difficult due to the strong electron-withdrawing effect. Therefore, this carbon-carbon bond formation reaction is remarkable from both mechanistic and synthetic aspects. 

Neighboring group and template effects. Promotion of nucleophilic substitution. 

Neighboring group participation effects appear to play a crucial role in the nucleophilic substitution of chlorine in Michael adducts of 1-R, 2-R, 3-X. Thus, this substitution proceeds very easily in any of the adducts formed with an electron rich nitrogen, sulfur and oxygen Michael donor. For the adducts of nitrogen nucleophiles, the facile substitution of the chlorine has been suggested to occur via formation of intermediate aziridinium ions 103 [8] (Scheme 32), and this postulate was later supported by isolation of azaspiropentane derivatives under appropriate conditions in several reactions (see Sect. 3.2.2) [11b, 53,56]. It is most likely that alkylthio substituents in adducts of type 85 participate in the same way to first form spirocyclopropane-annelated thiiranium ion intermediates which are subsequently opened by attack of the incoming nucleophile. 

Several other pyrolytic studies were performed on nylon 6. In one such study [4], the influence of several aliphatic carboxylates on nylon 6 thermal degradation was studied. The carboxylates that were evaluated include sodium butyrate, sodium caproate, sodium a-ethylcaproate, sodium caprylate, sodium laurate, potassium caproate, potassium laurate, and lithium caproate. Small amounts of these aliphatic carboxylates strongly increase the thermal decomposition rate even at 280° C. The effect of aliphatic carboxylates can be explained by the deprotonation of one of the amide groups of the polymer followed by the nucleophilic substitution of a neighboring carbonyl group, in a reaction as shown below ... 

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