Mechanisms of Nucleophilic Aliphatic Substitution

Pyridinium cations, role in mechanisms of nucleophilic aliphatic substitution 90CSR83. 

In following sections, we shall discuss the mechanisms of nucleophilic aliphatic substitution and of elimination using alkyl halides as our examples. But we should realize that these reactions take place in exactly the same ways with a variety of other compounds compounds which, like alkyl halides, contain good leaving groups. 

Nucleophilic Substitution in Haloalkanes Mechanisms of Nucleophilic Aliphatic Substitution Experimental Evidence for S 1 and S 2 Mechanisms Analysis of Several Nucleophilic Substitution Reactions S-Elimination... 

Mechanisms for nucleophilic aliphatic substitution at glycosides, 41, 277 Mechanisms of hydrolysis and rearrangements of epoxides, 40, 247 Mechanisms of oxygenations in zeolites, 42, 225 Mechanisms, nitrosation, 19, 381... 

The mechanism shown in Reaction 4.7 is still widely accepted as one of the two general mechanisms for nucleophilic aliphatic substitution. It is widely accepted today because in the intervening years a large bulk of experimental evi-... 

Recognition of the duality of mechanism for nucleophilic aliphatic substitution, formulation of the mechanisms themselves, and analysis of the factors influencing competition between them—all are largely due to Sir Christopher Ingold (of University College, London) and the people who worked with him and this is only a fraction of their total contribution to the theory of organic chemistry. 

When Bunnett and Zahler [1] published their landmark review in 1951, only two mechanisms of nucleophilic aromatic substitution were known. These were the unimolecular S l process, typically observed with arenediazonium salts, as in Scheme 6.1, and the bimolecular S,.jAr pathway, which is shown in Scheme 6.2 involving substitution of a halide ion by an anionic nucleophile and involving an anionic intermediate (1). As in aliphatic substitutions, both unimolecular and bimolecular pathways are possible. 

A more detailed classification of chemical reactions will give specifications on the mechanism of a reaction electrophilic aromatic substitution, nucleophilic aliphatic substitution, etc. Details on this mechanism can be included to various degrees thus, nucleophilic aliphatic substitutions can further be classified into Sf l and reactions. However, as reaction conditions such as a change in solvent can shift a mechanism from one type to another, such details are of interest in the discussion of reaction mechanism but less so in reaction classification. 

Figure 3-22 shows a nucleophilic aliphatic substitution with cyanide ion as a nucleophile, i his reaction is assumed to proceed according to the S f2 mechanism with an inversion in the stereochemistry at the carbon atom of the reaction center. We have to assign a stereochemical mechanistic factor to this reaction, and, clearly, it is desirable to assign a mechanistic factor of (-i-1) to a reaction with retention of configuration and (-1) to a reaction with inversion of configuration. Thus, we want to calculate the parity of the product, of 3 reaction from the parity of the... 

A. R. Katritzky, B. E. Brycki, The Mechanisms of Nucleophilic Substitution in Aliphatic Compounds, ... 

Nucleophilic substitution reactions on unactivated alkyl halides have been known for a long time. The available mechanisms depend on the aliphatic moiety, the nucleophile, the leaving group and the reaction conditions118. Besides the polar mechanisms of nucleophilic substitution reactions (S l, S 2 and related mechanisms), several alkyl halides react with nucleophiles by an ET reaction. 

That is, the act of shifting the single electron from Y to X may occur either with or without free-radical formation. Usually, the concerted non-radicaloid process is energetically favoured. For a more detailed discussion of the various mechanisms of nucleophilic substitution reactions in aliphatic compounds and their solvent dependence, see references [14, 483, 782-785]. 

Although the mechanism is not understood, evidence strongly suggests this much the alkyl group R is transferred from copper, taking a pair of electrons with it, and attaches itself to the alkyl group R by pushing out halide ion (nucleophilic aliphatic substitution. Sec. 14.9). 

In al this we have estimated the stability of a carbonium ion on the same basis the dispersal or concentration of the charge due to electron release or electron withdrawal by the substituent groups. As wc shall see, the approach that has worked so well for elimination, for addition, and for electrophilic aromatic substitution works for still another important class of organic reactions in which a positive charge develops nucleophilic aliphatic substitution by the S l mechanism (Sec. 14.14). It works equally well for nucleophilic aromatic substitution (Sec. 25.9), in which a negative charge develops. Finally, we shall find that this approach will help us to understand acidity or basicity of such compounds as carboxylic acids, sulfonic acids, amines, and phenols. 

This duality of mechanism does not reflect exceptional behavior, but is usual for electrophilic aromatic substitution. It also fits into the usual pattern for nucleophilic aliphatic substitution (Sec. 14.16), which—from the standpoint of the alkyl halide—is the kind of reaction taking place. Furthermore, the particular halides (T and methyl) which appear to react by this second mechanism are just the ones that would have been expected to do so. 

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