Leaving groups, nucleophilic displacement

In this chapter, S 2 reaction mechanisms were defined and presented in the context of nucleophiles displacing leaving groups at electrophilic centers. Furthermore, the conditions required for Sn2 reactions to proceed were discussed as well as factors that influence the progression of such reactions. In this context, discussions of SN2 reactions were extended into the related Sk2 reaction mechanisms. 

In some respects, the alkylation of enolate anions resembles nucleophilic substitution. We recall that many nucleophiles displace leaving groups from primary alkyl halides by an Sj 2 mechanism (Section 9.3). A similar reaction occurs with secondary alkyl halides, but competing elimination reactions also occur. Primary alkyl halides react with carbanions, such as the alkynide ion, by an Sj 2 mechanism. (Secondary alkyl halides react not only in displacement reactions but also in elimination reactions because the alkynide ion is a strong base.)... 

Representative organic syntheses. A solution of the naked fluoride ion may be generated by dissociation of KF in an acetonitrile or benzene solution containing 18-crown-6 (Liotta Harris, 1974). The considerable nucleophilicity of this anion under these conditions is demonstrated by the fact that it is capable of displacing leaving groups from both sp2 and sp3 hybridized carbons in a number of structural environments. 

Preparation of nitriles Cyanide ion (CN ) is a good nucleophile, and can displace leaving groups from 1° and 2° alkyl halides. Nitriles are prepared hy the treatment of alkyl halides with NaCN or KCN in dimethyl sulphoxide (DMSO). The reaction occurs rapidly at room temperature. 

Preparation of alkyl azides The azide ion (N3 ), a good nucleophile, can displace leaving groups from 1° and 2° alkyl halides. Alkyl azides are easily prepared from sodium or potassium azides and alkyl halides. The reaction mechanism resemhles the formation of nitrile. 

Nucleophilicity and leaving group ability 211 Effect of solvation on the gas-phase reaction 212 Mechanism of the gas-phase SN2 reaction 213 Potential energy surfaces for gas-phase SN2 reactions 214 Recent theoretical developments 218 Some examples of gas-phase SN2 reactions involving positive ions 220 Nucleophilic displacement reactions by negative ions in carbonyl systems 222 General features 222... 

The nature of the solvent and the structures of the substrate, nucleophile, and leaving group all help determine whether a nucleophilic displacement proceeds by a unimolecular or bimolecular pathway. They also all affect the rate of reaction. 

Nucleophilic substitution nucleophile (Nu-) seeks a "+" center (C of R group or >C=0), displaces leaving group -L. SN1 and SN2 mechanisms... 

Formation and Reduction of Azides Azide ion ( N3) is an excellent nucleophile that displaces leaving groups from unhindered primary and secondary alkyl halides and tosylates. The products are alkyl azides (RN3), which have no tendency to react further. Azides are easily reduced to primary amines, either by LiAlH4 or by catalytic hydrogenation. Alkyl azides can be explosive, so they are reduced without purification. 

The stereochemistry of the SN2 reaction has been shown to be variously syn (the nucleophile and leaving group are on the same face of the ally lie system) or anti, depending on the nature of the nucleophile and leaving group. For example, the cis isomer 26 with piperidine gave 27, in a clean syn allylic displacement, whereas Na+-SPr gave a ca. 2 1 mixture of isomers in which the trans isomer 28 was the major product. This trend toward anti substitution with RS- is more pronounced (almost exclusive) in the acyclic case 29. 

Inspection of equations la and lb shows that AE0 can be derived for any reaction if AE and AE° are known. One uniquely interesting aspect of the intrinsic activation energy is that it is equal for the forward and back directions. Thus, AE0 for X- + CH3Y is identical with AE0 for Y- + CH3X. Immediately, the distinction between nucleophile and leaving group in nucleophilic displacement reactions is removed. This consequence of the theory is one of the most powerful and useful. 

If an organic chemist wanted to put a methyl group on a nucleophile, methyl iodide would most likely be the methylating agent used. Of the methyl halides, methyl iodide has the most easily displaced leaving group because 1 is the weakest base of the halide ions. In addition, methyl iodide is a liquid, so it is easier to handle than methyl bromide or methyl chloride. The reaction would be a simple Sn2 reaction. 

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