Aliphatic carbon, nucleophilic substitution reaction mechanisms

Several distinct mechanisms are possible for aliphatic nucleophilic substitution reactions, depending on the substrate, nucleophile, leaving group, and reaction conditions. In all of them, however, the attacking reagent carries the electron pair with it, so that the similarities are greater than the differences. Mechanisms that occur at a saturated carbon atom are considered first. By far the most common are the SnI and Sn2 mechanisms. 

Many theories have been put forward to explain the mechanism of inversion. According to the accepted Hugles, Ingold theory aliphatic nucleophilic substitution reactions occur eigher by SN2 or SN1 mechanism. In the SN2 mechanism the backside attack reduces electrostatic repulsion in the transition state to a minimum when the leaving meleophile leaves the asymmetric carbon, naturally an inversion of configuration occurs at the central carbon atom. 

The measured half-lives range from 19 sec to 7000 yr, suggesting that structure variation can have significant effects on hydrolysis rates. The reactivity of these chemicals can be rationalized in terms of the limiting mechanisms presented for nucleophilic substitution. It is apparent from the data in Table 2.2 that the fluori-nated aliphatics are much more stable than the chlorinated aliphatics, which in turn are more stable than the brominated aliphatics. This trend in reactivity reflects the strength of the carbon-halogen bond, which follows the order F>Cl>Br, that is broken in the nucleophilic substitution reaction. 

As noted in Chapter 9, conventional nucleophilic substitution reactions of the type described for aliphatic compounds don t occur at sp hybrid carbon atoms. The formation of aryl cations is disfavored because they are unstable, and attack from the backside of the C-halogen bond is rendered impossible by the ring structure. So the substitution of aryl halides is much more difficult, and the mechanism of the S).j2Ar reaction is quite different, involving addition followed by elimination—a two-step process. For example, although substitution of chlorobenzene by hydroxyl ion is possible, conditions are harsh (350 °C, high pressure), and even then, yields are low. The reaction (Figure 13.13) probably involves a benzyne intermediate (see Sections 10.9 and 13.6). 

Nucleophilic aliphatic substitution (Chapter 8) Reaction m which a nucleophile replaces a leaving group usually a halide ion from sp hybridized carbon Nucleophilic aliphatic substitution may proceed by either an S l or an Sfj2 mechanism... 

In Part 2 of this book, we shall be directly concerned with organic reactions and their mechanisms. The reactions have been classified into 10 chapters, based primarily on reaction type substitutions, additions to multiple bonds, eliminations, rearrangements, and oxidation-reduction reactions. Five chapters are devoted to substitutions these are classified on the basis of mechanism as well as substrate. Chapters 10 and 13 include nucleophilic substitutions at aliphatic and aromatic substrates, respectively, Chapters 12 and 11 deal with electrophilic substitutions at aliphatic and aromatic substrates, respectively. All free-radical substitutions are discussed in Chapter 14. Additions to multiple bonds are classified not according to mechanism, but according to the type of multiple bond. Additions to carbon-carbon multiple bonds are dealt with in Chapter 15 additions to other multiple bonds in Chapter 16. One chapter is devoted to each of the three remaining reaction types Chapter 17, eliminations Chapter 18, rearrangements Chapter 19, oxidation-reduction reactions. This last chapter covers only those oxidation-reduction reactions that could not be conveniently treated in any of the other categories (except for oxidative eliminations). 

The essential features of the mechanism for aliphatic nucleophilic substitution at tertiary carbon were established in studies by Hughes and Ingold." ° However, as chemists probed more deeply, the problems associated with the characterization of borderline reaction mechanisms were encountered, and controversy remains to this day about whether these problems have been entirely solved." What is generally accepted is that ferf-butyl derivatives undergo borderline solvolysis reactions through a ferf-butyl carbocation intermediate that is too unstable to diffuse freely through nucleophilic solvents such as methanol and water. The borderline nature of substitution reactions at tertiary carbon is exemplihed by the following observations. 

The Sn2 reaction involves the attack of a nucleophile from the side opposite the leaving group and proceeds with exclusive inversion of configuration in a concerted manner. In contrast to the popular bimolecular nucleophilic substitution at the aliphatic carbon atom, the SN2 reaction at the vinylic carbon atom has been considered to be a high-energy pathway. Textbooks of organic chemistry reject this mechanism on steric grounds [175]. 

The author believes that students are well aware of the basic reaction pathways such as substitutions, additions, eliminations, aromatic substitutions, aliphatic nucleophilic substitutions and electrophilic substitutions. Students may follow undergraduate books on reaction mechanisms for basic knowledge of reactive intermediates and oxidation and reduction processes. Reaction Mechanisms in Organic Synthesis provides extensive coverage of various carbon-carbon bond forming reactions such as transition metal catalyzed reactions use of stabilized carbanions, ylides and enamines for the carbon-carbon bond forming reactions and advance level use of oxidation and reduction reagents in synthesis. 

The familiar substitution reactions of derivatives of carboxylic acids with basic reagents illustrate nucleophihc substitution at aliphatic sp carbons. (Substitution reactions of carboxylic acids, and their derivatives, with acidic reagents are covered in Chapter 4.) The mechanisms of these reactions involve two steps (1) addition of the nucleophile to the carbonyl group and (2) elimination of some other group attached to that carbon. Common examples include the basic hydrolysis and aminolysis of acid chlorides, anhydrides, esters, and amides. 

The S l mechanism of this type permits substitution of certain aromatic and aliphatic nitro compounds by a variety of nucleophiles. These reactions were discovered as the result of efforts to understand the mechanistic basis for high-yield carbon alkylation of the 2-nitropropane anion by p-nitrobenzyl chloride. The corresponding... 

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