Elimination Reactions Zaitsevs Rule

We began this chapter by saying that two kinds of reactions can happen when a nucleophile/Lewis base reacts with an alkyl halide. The nucleophile can either substitute for the halide by reaction at carbon or can cause elimination of HX by reaction at a neighboring hydrogen  

Elimination reactions are more complex than substitution reactions for several reasons. There is, for instance, the problem of regiochemistry what products result by loss of HX from an nnsymmetrical halide In fact, elimination reactions almost always give mixtures of alkene products, and the best we can usually do is to predict which will be the major product. 

According to Zaitsev s rule, formulated in 1875 by the Russian chemist Alexander Zaitsev, base-induced ehmination reactions generally (although not always) give the more stable alkene product—that is, the alkene with more alkyl substituents on the double-bond carbons. In the following two cases, for example, the more highly substituted alkene product predominates. 

In the elimination of HX from an alkyl halide, the more highly substituted alkene product predominates. 

El Reaction C-X bond breaks first to give a carbocation intermediate, followed by base removal of a proton to yield the alkene. 

Test your knowledge of Key Ideas by answering end-of-chapter exercises marked with A. 

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Zaitsev rule (Section 8.5) In a P elimination reaction, a rule that states that the major product is the alkene with the most substituted double bond. 

Zaitsev s rule as applied to the acid catalyzed dehydration of alcohols is now more often expressed in a different way elimination reactions of alcohols yield the most highly substituted alkene as the major product Because as was discussed in Section 5 6 the most highly substituted alkene is also normally the most stable one Zaitsev s rule is sometimes expressed as a preference for predominant formation of the most stable alkene that could arise by elimination... 

The least sterically hindered p hydrogen is removed by the base m Hofmann elim matron reactions Methyl groups are deprotonated m preference to methylene groups and methylene groups are deprotonated m preference to methmes The regioselectivity of Hofmann elimination is opposite to that predicted by the Zaitsev rule (Section 5 10) Elimination reactions of alkyltrimethylammonmm hydroxides are said to obey the Hofmann rule, they yield the less substituted alkene... 

Zaitsevs rule (Section 5 10) When two or more alkenes are capable of being formed by an elimination reaction the one with the more highly substituted double bond (the more sta ble alkene) is the major product Zwitterion (Section 27 3) The form in which neutral amino acids actually exist The ammo group is in its protonated form and the carboxyl group is present as a carboxylate... 

With a regioselectivity opposite to that of the Zaitsev rule, the Hofmann elimination is sometimes used in synthesis to prepare alkenes not accessible by dehydrohalo-genation of alkyl halides. This application decreased in importance once the Wittig reaction (Section 17.12) becfflrre established as a synthetic method. Similarly, most of the analytical applications of Hofmann elimination have been replaced by spectroscopic methods. 

Elimination Reactions of Alkyl Halides Zaitsev s Rule 383... 

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. 

Zaitsev s rule (Section 11.7) A rule stating that E2 elimination reactions normally yield the more highly substituted alkene as major product. 

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. 

Zaitsev s rule states that the major product in the formation of alkenes by elimination reactions will be the more highly substituted alkene, or the alkene with more substituents on the carbon atoms of the double bond. 

It is possible to predict which product will be formed in larger amounts in these reactions. Most E2 elimination reactions follow 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. 

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. 

ZAITSEV S RULE In elimination reactions, the most substituted alkene usually predominates. 

The Zaitsev rule applies to El reactions, too. For example, El elimination of HBr from 1-bromo-1-methylcyclopentane yields alkenes A and B. A, having the more substituted double bond, is the major product. 

Figure 25.11 contrasts the products formed by E2 elimination reactions using an alkyl halide and an amine as starting materials. Treatment of the alkyl halide (2-bromopentane) with base forms the more substituted alkene as the major product, following the Zaitsev rule. In contrast, the three-step Hofmann sequence of an amine (2-pentanamine) forms the less substituted alkene as major product. 

Another piece of evidence involves the stereochemistry of elimination. Unlike the E2 reaction, where periplaiiar geometiy 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 (Zaitsevs rule) product from El reaction, which is just what we find. To return to a familiar example, menthyl chloride loses HCl under El conditions in a polar solvent to give a mixture of alkenes in which the Zaitsev product, 3-menthene, predominates (Figure 11.22). 

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