Between Substitution and Elimination

It is an axiom of organic chemistry that substitution and elimination reactions are competitive processes. Elimination is generally favored at higher temperatures, while lower temperatures result in a higher percentage of substitution product in both El and E2 reactions. Eor example, in the solvolysis of f-butyl chloride in 80% aqueous ethanol, the percentage of isobutene 

Calculated potential energy surface for the elimination reaction in equation 10.23. (Reproduced from reference 37.) 

Elimination becomes more competitive with substitution as the number of alkyl substituents on the substrate increases. Table 10.2 shows rate constants for Sn2 and E2 reactions of a series of alkyl bromides with sodium ethoxide in ethanol at 55°C. The rate constant for elimination increases along the series from ethyl bromide to propyl bromide to isobutyl bromide. The more substituted alkenes formed with propyl bromide and (to a greater extent) with isobutyl bromide are more stable than the alkene formed from ethyl bromide. Because the transition structures have some double bond 

TABLE 10.1 Activation Parameters for Substitution and Elimination Reactions  

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Section 8 13 When nucleophilic substitution is used for synthesis the competition between substitution and elimination must be favorable However the normal reaction of a secondary alkyl halide with a base as strong or stronger than hydroxide is elimination (E2) Substitution by the Sn2 mechanism predominates only when the base is weaker than hydroxide or the alkyl halide is primary Elimination predominates when tertiary alkyl halides react with any anion... 

Now let s consider the effect of the substrate on the rate of an E2 process. Recall from the previous chapter that Sn2 reactions generally do not occur with tertiary substrates, because of steric considerations. But E2 reactions are different than Sn2 reactions, and in fact, tertiary substrates often undergo E2 reactions quite rapidly. To explain why tertiary substrates will undergo E2 but not Sn2 reactions, we must recognize that the key difference between substitution and elimination is the role played by the reagent. In a substitution reaction, the reagent functions as a nucleophile and attacks an electrophilic position. In an elimination reaction, the reagent functions as a base and removes a proton, which is easily achieved even with a tertiary substrate. In fact, tertiary substrates react even more rapidly than primary substrates. 

An El reaction is generally accompanied by a competing SnI reaction, and a mixture of products is generally obtained. At the end of this chapter, we will explore the main factors that affect the competition between substitution and elimination reactions. 

Nakai, T. Tanaka, K. Ishikawa, N. The reaction of 2,2,2-trifluoroethyl iodide with sodium phenolate. A novel competition between substitution and elimination reactions. /. Fluorine Chem. 1977, 9, 89-93. 

S. Gronert, Gas-Phase Studies of the Competition between Substitution and Elimination Reactions, Ace, Chem. Res. 2003, 36, 848-857. 

Elimination reactions are a useful method for the preparation of alkenes, provided that certain limitations are recognized. One problem is the competition between substitution and elimination. The majority of eliminations are done under conditions that favor the E2 mechanism. In these cases, steric hindrance can be used to slow the competing SN2 pathway. Tertiary substrates and most secondary substrates give good yields of the elimination product when treated with strong bases. Sterically hindered bases can be employed with primary substrates to minimize substitution. 

The least expensive method for synthesizing simple symmetrical ethers is the acid-catalyzed bimolecular condensation (joining of two molecules, often with loss of a small molecule like water), discussed in Section 11-10B. Unimolecular dehydration (to give an alkene) competes with bimolecular condensation. To form an ether, the alcohol must have an unhindered primary alkyl group, and the temperature must not be allowed to rise too high. If the alcohol is hindered or the temperature is too high, the delicate balance between substitution and elimination shifts in favor of elimination, and very little ether is formed. Bimolecular condensation is used in industry to make symmetrical ethers from primary alcohols. Because the condensation is so limited in its scope, it finds little use in the laboratory synthesis of ethers. 

The factors which affect the balance between substitution and elimination reactions... 

Katritzky and coworkers have extensively developed the activation of amines by reaction with pyry-lium salts to provide (V-alkyl (or N-aryl) pyridinium compounds. When buttressing substituents were present to discourage attack on the pyridine ring, the N-alkyl substituent was subject to displacement and elimination processes. In general, primary alkyl substituents reacted with most nucleophiles in a normal 5n2 process as shown in Scheme 12, whereas competition between substitution and elimination took place with the secondary analogs, with elimination dominating the reactions starting from cycloalkyl-amines. 

Let us return to a problem we encountered before, in the reaction between acetyiides and alkyl halides (Sec. 8.12) competition between substitution and elimination. Both reactions result from attack by the same nucleophilic reagent attack at carbon causes substitution, attack at hydrogen causes elimination. 

The product of a substitution reaction that follows the limiting Sf 2 mechanism is determined by the identity of the nucleophile. The nucleophile replaces the leaving group and product mixtures are obtained only if there is competition from several nucleophiles. Product mixtures from ionization mechanisms are often more complex. For many carbocations there are two competing processes that lead to other products elimination and rearrangement. We discuss rearrangements in the next section. Here we consider the competition between substitution and elimination under solvolysis conditions. We return to another aspect of this competition in Section 5.10, when base-mediated elimination is considered. 

Elimination Reactions of Alkyl Halides Competition Between Substitution and Elimination... 

In the next section we shall discuss the competition between substitution and elimination reactions. To understand this competition it is important that you have acquired a good grasp of the mechanisms of substitution and elimination reactions. 

Part Z The Mechanism of Substitution and Part 3 Elimination and Addition Pathways and Products are concerned with organic reaction mechanisms. Curly arrows are introduced and the key features of the two common mechanisms of nucleophilic substitution are reviewed. Including kinetic features, stereochemical outcome and reaction coordinate diagrams. This leads to a discussion of the features of El and E2 elimination reactions. The book finishes with a discussion of the factors that affect the competition between substitution and elimination reactions. Much of the teaching of substitution mechanisms Is carried out via interactive CD-ROM activities. 

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