Nucleophilic Substitution at Carbon

Turning to bicyclic systems, and a study of reaction with ethoxide, a small increase in the rate of reaction relative to pyridines was found for chloroquinolines at comparable positions.In the bicyclic compounds, quaternisation again greatly increases the rate of nucleophilic substitution, having a larger effect ( 10 ) at C-2 

Diazines with halogen a and 7 to nitrogen are much more reactive than similar 

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Phosphate esters have a variety of mechanistic paths for hydrolysis. Both C-O and P-0 cleavage are possible depending on the situation. A phosphate monoanion is a reasonable leaving group for nucleophilic substitution at carbon and so 8 2 or SnI reactions of neutral phosphate esters are well known. PO cleavage can occur by associative (by way of a pentacoordinate intermediate), dissociative (by way of a metaphosphate species), or concerted (avoiding both of these intermediates) mechanisms. 

Apart from overcoming coulombic repulsions, 8 2 reactions also proceed with inversion in the face of steric hindrance. By comparison, the stereochemical result of unimolecular nucleophilic substitution SN1 is variable. In fact, nucleophilic substitutions at carbon with retention invariably follow other than SN2 paths. In its broad outlines, the Hughes-Ingold approach swept away the confusions of the period 1895-1933 and has not ceased to stimulate and provoke ideas in the area of substitution reactions. Surprisingly enough, the theoretical foundations of the SN2 process require reexamination and modification, as we shall see. 

The N—S bond can be cleaved by nucleophilic attack at the sulfur as a competitive or preferable reaction path to nucleophilic substitution at carbon. 

In this section, we note several other reactions which are formally nucleophilic substitutions at carbon. Because they fall outside of the mechanistic pattern of the rest of this chapter, their inclusion has been postponed to this point. 

Similar free radical substitution reactions can be effected with bromine (using, e.g., A-bromosuccinimide [NBS]) and, once the halogen is in place, nucleophilic substitution at carbon a to silicon (or indeed, elsewhere) occurs with relative ease. ... 

Carbon.— The suggestion that the mechanisms of nucleophilic substitution at carbon, 5n1 and 5 n2, might merge into an ion-pair mechanism has been further... 

Bento AP, Sola M, BickeUiaupt FM (2005) Ab initio and DFT benchmark smdy for nucleophilic substitution at carbon (Sn2 C) and silicon (Sn2 S0. J Comput Chem 26 1497-1504... 

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