Zaitsev reactions

Allylic, benzylic, propargylic, and related organic halides react with many aldehydes and ketones in the presence of zinc to form alcohols. This reaction (the Zaitsev reaction) has been used in the synthesis of alcohols containing unsaturated groups. For example,... 

Zaitsev reactions are the reaction that organic halides such as allyl halides, benzyl halides and propagyl halides react with aldehydes or ketones in the presence of zinc, and the product is hydrolyzed to give secondary or tertiary alcohols as shown in eq. (5.25)... 

Zaitsev reactions also proceed similar to the Reformatsky reactions. Namely, organozinc compounds are synthesized in advance, and subsequently they react with aldehydes or ketones. Therefore, addition to the carbonyl of arylzinc compounds as shown in eq. (5.15) is also known as the Zaitsev reaction. Not only the addition to the carbonyl group of aldehydes or ketones but also the addition to carbon—carbon double bonds are the related reactions of Zaitsev reactions as shown in eq. (5.26) [37]. 

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... 

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)... 

Dehydrohalogenation of alkyl halides (Sections 5 14-5 16) Strong bases cause a proton and a halide to be lost from adjacent carbons of an alkyl halide to yield an alkene Regioselectivity is in accord with the Zaitsev rule The order of halide reactivity is I > Br > Cl > F A concerted E2 reaction pathway is followed carbocations are not involved and rearrangements do not occur An anti coplanar arrangement of the proton being removed and the halide being lost characterizes the transition state... 

Markovnikov s rule like Zaitsev s organizes experimental observations in a form suitable for predicting the major product of a reaction The reasons why it works will appear when we examine the mechanism of electrophilic addition m more detail... 

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... 

According to Zaitsev s rule, formulated in 1875 by the Russian chemist Alexander Zaitsev, base-induced elimination 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. 

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. 

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. 

Here s an example how might we prove that E2 elimination of an alkyl halide gives the more highly substituted alkene (Zaitsev s rule, Section 11.7) Does reaction of 1-chloro-l-methylcyclohexane with strong base lead predominantly to 1-methyl cyclohexene or to methylenecyclohexane ... 

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. 

So if we look back at the reaction above, we find that the two possible prodncts are monosubstituted and disubstitnted donble bonds. Whenever we have an elimination reaction where more than one possible donble bond can be formed, we have names for the different products based on which one is more substitnted and which one is less substituted. The more substituted product is called the Zaitsev product, and the... 

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