Elimination and Zaitsev’s rule

Another problem that occurs with eliminations is the regiochemistry of the reaction. As we saw in Chapter 9, most eliminations follow Zaitsev s rule and produce the more highly substituted alkene as the major product. However, a significant amount of the less highly substituted product is also formed. In addition, mixtures of ds and trans isomers are produced when possible, further complicating the product mixture. Because separating a mixture of such isomers is usually a difficult task, elimination reactions are often not the best way to prepare alkenes. (Other methods will be described in subsequent chapters.) However, if only one product can be formed, or if one is expected to greatly predominate in the reaction mixture, then these elimination reactions can be quite useful. 

Alkenes are prepared by P elimination of alcohols and alkyl halides These reactions are summarized with examples m Table 5 2 In both cases p elimination proceeds m the direction that yields the more highly substituted double bond (Zaitsev s rule)... 

The anti periplanar requirement for E2 reactions overrides Zaitsev s rule and can be met in cyclohexanes only if the hydrogen and the leaving group are trans diaxial (Figure 11.19). If either the leaving group or the hydrogen is equatorial, E2 elimination can t occur. 

The difference in reactivity between the isomeric menthyl chlorides is due to the difference in their conformations. Neomenthyl chloride has the conformation shown in Figure 11.20a, with the methyl ancl isopropyl groups equatorial and the chlorine axial—a perfect geometry for L2 elimination. Loss of the hydrogen atom at C4 occurs easily to yield the more substituted alkene product, 3-menthene, as predicted by Zaitsev s rule. 

A final piece of evidence involves the stereochemistry of elimination. (Jnlike the E2 reaction, where anti periplanar geometry is required, there is no geometric requirement on the El reaction because the halide and the hydrogen are lost in separate steps. We might therefore expect to obtain the more stable (Zaitsev s rule) product from El reaction, which is just what w e find. To return to a familiar example, menthyl chloride loses HC1 under El conditions in a polar solvent to give a mixture of alkenes in w hich the Zaitsev product, 3-menthene, predominates (Figure 11.22). 

Practically everything we ve said in previous chapters has been stated without any proof. We said in Section 6.8, for instance, that Markovnikov s rule is followed in alkene electrophilic addition reactions and that treatment of 1-butene with HC1 yields 2-chJorobutane rather than 1-chlorobutane. Similarly, we said in Section 11.7 that Zaitsev s rule is followed in elimination reactions and that treatment of 2-chlorobutane with NaOH yields 2-butene rather than 1-butene. But how do we know that these statements are correct The answer to these and many thousands of similar questions is that the structures of the reaction products have been determined experimentally. 

However, the E2C mechanism has been criticized, and it has been contended that all the experimental results can be explained by the normal E2 mechanism. McLennan suggested that the transition state is that shown as 18. An ion-pair mechanism has also been proposed. Although the actual mechanisms involved may be a matter of controversy, there is no doubt that a class of elimination reactions exists that is characterized by second-order attack by weak bases. " These reactions also have the following general characteristics (1) they are favored by good leaving groups (2) they are favored by polar aprotic solvents (3) the reactivity order is tertiary > secondary > primary, the opposite of the normal E2 order (p. 1319) (4) the elimination is always anti (syn elimination is not found), but in cyclohexyl systems, a diequatorial anti elimination is about as favorable as a diaxial anti elimination (unlike the normal E2 reaction, p. 1302) (5) they follow Zaitsev s rule (see below), where this does not conflict with the requirement for anti elimination. 

Tertiary halides undergo elimination most easily. Eliminations of chlorides, bromides, and iodides follow Zaitsev s rule, except for a few cases where steric effects are important (for an example, see p. 1316). Eliminations of fluorides follow Hofmann s rule (p. 1316). 

The E2 elimination needs the presence of a [3-p roton. If there are various options available, a mixture of alkenes will be obtained, but the favoured alkene will be the most substituted (and most stable) one (Zaitsev s rule) ... 

Using Zaitsev s Rule and Hofmann s Rule to Predict Elimination Products... 

For eliminations, form the carbon-carbon double bond according to Zaitsev s rule (except the Hofmann elimination) and use anti elimination to determine the stereochemistry of E2 reactions. 

Zaitsev s rule (Section 9.4) The major product of an elimination reaction is the alkene with more alkyl groups on the carbons of the double bond (the more highly substituted product). Most El and E2 reactions follow this rule. 

The first product has a trisubstituted double bond, with three substituents (circled) on the doubly bonded carbons. It has the general formula R2C=CHR. The second product has a disubstituted double bond, with general formula R2C=CH2 (or R—CH=CH—R). In most El and E2 eliminations where there are two or more possible elimination products, the product with the most substituted double bond will predominate. This general principle is called Zaitsev s rule, and reactions that give the most substituted alkene are said to follow Zaitsev orientation. 

Predict the products of SnI, Sn2, El, and E2 reactions, including stereochemistry. Use Zaitsev s rule to predict the major and minor products of eliminations. 

The substrate is tertiary, and the nucleophiles are basic. Two elimination products are expected the major product has the more substituted double bond, in accordance with Zaitsev s rule. 

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