Alkyl halides, from nucleophilic substitution reactions

To check this possibility we performed experiments with different concentrations of NaBr in the NaY zeolite. Table 2 presents the results. It can be seen that upon increasing the amount of NaBr impregnated on NaY, there is preference to formation of the cyclobutyl bromide over allylcarbinyl bromide, indicating that the relative position between the bromide ions and bicyclobutonium governs the product distribution. Hence, zeolites may act as solid solvent, favoring ionization of alkyl halides and nucleophilic substitution reactions. In contrast to liquid solvents, where solvation is mostly uniform, the zeolite surface seems to provide unsymmetrical solvation of the cations, leading to product distribution that is different from solution. 

Alkylation of Ammonia Salts of primary amines can be prepared from ammonia and alkyl halides by nucleophilic substitution reactions. Subsequent treatment of the resulting aminium salts with a base gives primary amines ... 

Alkyl halides undergo nucleophilic substitution reactions, in which a nucieophiie dispiaces the haiide leaving group from the aikyi haiide substrate. 

Basic, electron-rich reagents are called nucleophilic reagents (from the Greek, nucleus-loving). The typical reaction of alkyl halides is nucleophilic substitution ... 

It is not immediately obvious how to carry out this synthesis, so let s use retrosynthetic analysis to find a way. The only method you know for introducing a C=N group into a molecule is nucleophilic substitution. The alkyl halide for that substitution reaction can be obtained from die addition of HBr to an alkene in the presence of a peroxide. The alkene for that addition reaction can be obtained from an elimination reaction using an alkyl halide obtained by benzylic substitution. 

The reactions of alcohols with hydrogen halides to give alkyl halides (Chapter 4) are nucleophilic substitution reactions of alkyloxonium ions m which water is the leaving group Primary alcohols react by an 8 2 like displacement of water from the alkyloxonium ion by halide Sec ondary and tertiary alcohols give alkyloxonium ions which form carbo cations m an S l like process Rearrangements are possible with secondary alcohols and substitution takes place with predominant but not complete inversion of configuration... 

Sulfonate esters are especially useful substrates in nucleophilic substitution reactions used in synthesis. They have a high level of reactivity, and, unlike alkyl halides, they can be prepared from alcohols by reactions that do not directly involve bonds to the carbon atom imdeigoing substitution. The latter aspect is particularly important in cases in which the stereochemical and structural integrity of the reactant must be maintained. Sulfonate esters are usually prepared by reaction of an alcohol with a sulfonyl halide in the presence of pyridine ... 

From this and nearly a dozen other series of similar reactions, workers concluded that the nucleophilic substitution reaction of a primary or secondary alkyl halide or tosylate always proceeds with inversion of configuration. (Tertiary alkyl halides and tosylates, as we ll see shortly, give different stereochemical results and react by a different mechanism.)... 

How- does this reaction take place Although it appears superficially similar to the SN1 and S 2 nucleophilic substitution reactions of alkyl halides discussed in Chapter 11, it must be different because aryl halides are inert to both SN1 and Sj 2 conditions. S l reactions don t occur wdth aryl halides because dissociation of the halide is energetically unfavorable due to tire instability of the potential aryl cation product. S]sj2 reactions don t occur with aryl halides because the halo-substituted carbon of the aromatic ring is sterically shielded from backside approach. For a nucleophile to react with an aryl halide, it would have to approach directly through the aromatic ring and invert the stereochemistry of the aromatic ring carbon—a geometric impossibility. 

Many of the reactions of amines are familiar from past chapters. Thus, amines react with alkyl halides in S 2 reactions and with acid chlorides in nucleophilic acyl substitution reactions. Amines also undergo E2 elimination to yield alkenes if they are first qualernized by treatment with iodomethane and then heated with silver oxide, a process called the Hofmann elimination. 

Polymeric phosphonium salt-bound carboxylate, benzenesulphinate and phenoxide anions have been used in nucleophilic substitution reactions for the synthesis of carboxylic acid esters, sulphones and C/O alkylation of phenols from alkyl halides. The polymeric reagent seems to increase the nucleophilicity of the anions376 and the yields are higher than those for corresponding polymer phase-transfer catalysis (reaction 273). 

Although a substantial number of reactions are described in the text, they belong to a relatively modest number of mechanistic types. The preparation of alkyl halides from alcohols and HX, the cleavage of ethers, and the preparation of amines from alkyl halides and ammonia (and many other reactions) all, for example, occur by a nucleophilic substitution mechanism. The following is a brief review of the main mechanistic pathways discussed in the text. 

Nucleophilic substitutions reactions are those reactions in which the substitution of one nucleophile for another is involved. Alkyl halides, carboxylic acids, and carboxylic acid derivatives undergo nucleophilic substitution. However, the mechanisms involved for alkyl halides are quite different from those involved for carboxylic acids and their derivatives. The reaction of a methoxide ion with ethanoyl chloride is a nucleophilic substitution reaction (Following fig.). In it one nucleophile (the methoxide ion) substitutes another nucleophile Cl. ... 

Fig. 2. Examples of nucleophilic substitution reactions performed in microemulsions. Scheme 1 synthesis of decyl sulfonate from decyl bromide and hydrogen sulfite. Scheme 2 synthesis of 2-hydroxyoctyl sulfonate from 1,2-epoxyoctane and hydrogen sulfite. Scheme 3 reaction of 4-nitrobenzylpyridine (NBP) with an alkyl halide (RX) followed by alkaline hydrolysis of the N-alkyl derivative (NBP-R+) formed. Scheme 4 a reaction involving displacement of the trinitrophenoxide ion by bromide...

In the elimination (a dehydrohalogenation), the reagent (BT) reacts as a base, abstracting a proton from the alkyl halide. Most nucleophiles are also basic and can engage in either substitution or elimination, depending on the alkyl halide and the reaction conditions. 

We take up the aryl halides in a separate chapter because they differ so much from the alkyl halides in their preparation and properties. Aryl halides as a class are comparatively unreactive toward the nucleophilic substitution reactions so characteristic of the alkyl halides. The presence of certain other groups on the aromatic ring, however, greatly increases the reactivity of aryl halides in the absence of such groups, reaction can still be brought about by very basic reagents or high temperatures. We shall find that nucleophilic aromatic substitution can follow two very different paths the bimolecular displacement mechanism for activated aryl halides and the elimination-addition mechanismy which involves the remarkable intermediate called benzyne. 

Because of the great versatility of nucleophilic substitution reactions many kinds of products can be prepared from alkyl halides. Table 11.1 lists some common nucleophiles in the approximate order of their reactivity am shows the products of their reactions with bromom ethane. 

Other substitution reactions we ve seen include some of the reactions used for preparing alkyl halides from alcohols. We said in Section 10.7, for example, that alkyl halides can be prepared by treating alcohols with HX—reactions now recognizable as nucleophilic substitutions of halide on the protonated alcohols. Tertiary alcohols react by an S>jl pathway involving unimolecular dissociation of the protonated alcohol to yield a carbo-cation, whereas primary alcohols react by an 8 2 pathway involving direct bimolecular displacement of H2O from the protonated alcohol (Figure 11.23). 

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