I Reactions of Alkyl Halides Nucleophilic Substitutions and Eliminations

CHAPTER 11 I Reactions of Alkyl Halides Nucleophilic Substitutions and Eliminations... 

These two reactions, dehydration and the formation of an alkyl halide, also fiunish another example of the competition between nucleophilic substitution and elimination (see Section 6.18). Very often, in conversions of alcohols to alkyl halides, we find that the reaction is accompanied by the formation of some alkene (i.e., by elimination). The free energies of activation for these two reactions of carbocations are not very different from one another. Thus, not all of the carbocations become stable products by reacting with nucleophiles some lose a j8 proton to form an alkene. 

Cutting Edge Content—The chapters on nucleophilic substitution and elimination have been rewritten to incorporate the new finding that secondary alkyl halides do not undergo S l/El reactions. You will be surprised at how much easier the addition of this one new fact makes this topic. I feel badly that students have been tortured for so long by misinformation ... 

El eliminations begin with the same unimolecular dissociation we saw in the Sfreactions normally occur together whenever an alkyl halide is treated in a protic solvent with a non-basic nucleophile. Thus, the best El substrates are also the best S <1 substrates, and mixtures of substitution and elimination products are usually obtained. For example, when 2-chloro-2-mcthylpropane is warmed tc 65 °C in 80% aqueous ethanol, a 64 36 mixture of 2-methvi-2-propanol (Sj,jT) and 2-mcthylpropene (F1) results. 

Key point. Alkyl halides are composed of an alkyl group bonded to a halogen atom (X = F, Cl, Br, I). As halogen atoms are more electronegative than carbon, the C-X bond is polar and nucleophiles can attack the slightly positive carbon atom. This leads to the halogen atom being replaced by the nucleophile in a nucleophilic substitution reaction, and this can occur by either an SN1 (two-step) mechanism or an Sn2 (concerted or one-step) mechanism. In competition with substitution is elimination, which results in the loss of HX from alkyl halides to form alkenes. This can occur by either an El (two-step) mechanism or an E2 (concerted) mechanism. The mechanism of the substitution or elimination reaction depends on the alkyl halide, the solvent and the nucleophile/base. 

The acetylide ion is a strongly basic and nucleophilic species which can induce nucleophilic substitution at positive carbon centres. Acetylene is readily converted by sodium amide in liquid ammonia to sodium acetylide. In the past alkylations were predominantly carried out in liquid ammonia. The alkylation of alkylacetylenes and arylacetylenes is carried out in similar fashion to that of acetylene. Nucleophilic substitution reactions of the alkali metal acetylides are limited to primary halides which are not branched in the -position. Primary halides branched in the P-position as well as secondary and tertiary halides undergo elimination to olefins by the NaNH2. The rate of reaction with halides is in the order I > Br > Cl, but bromides are generally preferred. In the case of a,o)-chloroiodoalkanes and a,to-bromoiodoalkanes. 

The reactions of carbonimidoyl dihalides can be divided into nucleophilic substitution reactions, whereby the halo groups are replaced stepwise by other nucleophiles, and addition reactions. The substitution reactions are often accompanied by elimination, depending upon the stability of the formed imidoyl derivatives. For example, the monosubstitution products can eliminate hydrogen halide, alkyl halide, or sulfenyl chloride, i.e.,... 

Many other types of organic compounds can be conveniently prepared by nucleophilic substitution processes. These are exemplified in Scheme 5.4. It should be noted that the processes most used for synthetic transformations involve substrates that are reactive in the direct-displacement mechanism, i.e., primary and unhindered secondary alkyl halides and sulfonates. The tendency toward elimination in tertiary alkyl systems is sufficiently pronounced to limit the usefulness of nucleophilic substitution reactions in synthetic transformations involving these systems. 

It is postulated that thermal decomposition of tetra-alkylphosphonium salts proceeds through four types of reactions [42, 43] (i) nucleophilic substitution at the a-carbon (Sn(C)) (ii) (3-elimination (iii) nucleophilic substitution at the phosphorus atom (Sn(P)) (iv) a-elimination. Sn(C) nucleophilic substitution involves the attack of the halide on the a-carbon, leading to the formation of an alkyl halide and a tertiary phosphine ... 

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