The E2 Mechanism

Early synthetic observations illustrated the great preference for an anti-orientation of the elimination groups . In this conformation the electron pair released from the beta carbon hydrogen bond enters the C -octet on the side remote from the leaving group. Repulsion energy between the electron pairs is thus minimised in the transition state and by analogy to the known stereochemistry of Sn2 reactions, the Cg-H electrons are most favourably disposed 

The preference for a fi-stereospecificity is demonstrated experimentally in the acyclic series by use of suitable diastereoisomeric pairs. The we o-stilbene dibromide eliminates to give the cw-bromostilbene and the ( )-dibromide yields the rra j-olefin (77) .  

With the neutral base, trimethylamine, the threo and erythro isomers of 2-p-tolylsulphonyl-3-butyl brosylate exhibit a/ir/-elimination in aqueous dioxan .  

In ethanol containing ethoxide, the threo and erythro isomers of 1,2-diphenyl-1-propyl halides or trimethylammonium ion react in a similar stereochemical fashion , but in r-butyl alcohol containing r-butoxide, both the ammonium salts give the tra/i -olefin under kinetically controlled conditions . As both isomers have similar thermodynamic stabilities and react at similar rates, the anticipated comparable energies of the transition states have been attributed to the possible incursion of the ElcB mechanism . This seems unlikely as in the analogous elimination from the 2-phenylethyltrimethyl- 

Solvent I-BuOH QH50H CH3OH I-BuOH QH5OH 

What is the mechanism for elimination What is the order of bond breaking and bond making Is the reaction a one-step process or does it occur in many steps  

There are two mechanisms for elimination—E2 and El—just as there are two mechanisms for nucleophihc substitution—Sn2 and SnI. 

The E2 and El mechanisms differ in the tuning of bond cleavage and bond formation, analogous to the Sn2 and S l mechanisms. In fact, E2 and Sn2 reactions have some features in common, as do El and S l reactions. 

The most common mechanism for dehydrohalt enation is the E2 mechanism. For example, (CH3)3CBr reacts with OH to form (CH3)2C=CH2 via an E2 mechanism. 

An E2 reaction exhibits second-order kinetics that is, the reaction is bimolecular and both the alkyl halide and the base appear in the rate equation. 

Like the reaction mechanism, the E2 mechanism is a one step, concerted process. In an E2 dehy-drohalogenation reaction, the base removes a proton on a P-carbon atom adjacent to the carbon atom that contains the leaving group (the a-carbon). As the proton is removed, the leaving group departs, and a double bond forms. The transition state is shown for the general base, which is represented by Br (X represents the halide). The base in an E2 reaction is also a nucleophile, and we vtill see in Chapter 10 that Sj 2 reactions compete vtith E2 reactions. 

The carbon—hydrogen and carbon—halogen bonds are partially broken in the transition state, so the strength of the carbon-halogen bond affects the rate of the reaction. Alkyl iodides have the weakest carbon-halogen bond. Therefore, they react at the fastest rate. 

A partial double bond develops in the transition state for the E2 elimination. The partially formed double bond in the transition state is stabilized by alkyl groups just as the double bond of alkenes is stabilized by alkyl groups. Therefore, the transition state for the formation of the more substituted alkene has the lower energy barrier. 

In this section we explore the concerted mechanism, or E2, pathway  

Kinetic studies show that many elimination reactions exhibit second-order kinetics with a rate equation that has the following form  

Much like the Sn2 reaction, the rate is linearly dependent on the concentrations of two different compounds (the substrate and the base). This observation suggests that the mechanism must exhibit a step in which the substrate and the nucleophile collide with each other. This is consistent with a concerted mechanism in which there is only one mechanistic step involving both the substrate and the base. Because that step involves two chemical entities, it is said to be bimolecular. Bimolecular elimination reactions are called E2 reactions  

13 The following reaction exhibits a second-order rate equation  

A tertiary substrate is too sterically hindered. The nucleophile cannot penetrate and attack. 

In a substitution reaction, the leaving group is replaced with a nucleophile. In an elimination reaction, a beta ((3) proton is removed together with the leaving group, forming a double bond. In the previous chapter, we saw two mechanisms for substitution reactions (SnI and Sn2). In a similar way, we will now explore two mechanisms for elimination reactions, called El and E2. Let s begin with the E2 mechanism. 

In an E2 process, a base removes a proton, causing the simultaneous expulsion of a leaving group  

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. 

Problem 8.5 which alkene in each pair is more stable  

Problem 8.6 Several factors can affect alkene stability. Explain why alkene A is more stable than alkene B even though both contain disubstituted carbon-carbon double bonds. 

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The E2 mechanism is followed whenever an alkyl halide—be it primary second ary or tertiary—undergoes elimination m the presence of a strong base... 

Use curved arrows to track electron movement in the dehydro halogenation of tert butyl chloride by sodium methoxide by the E2 mechanism J... 

The regioselectivity of elimination is accommodated m the E2 mechanism by noting that a partial double bond develops at the transition state Because alkyl groups... 

Further insight into the E2 mechanism comes from stereochemical studies One such experiment compares the rates of elimination of the cis and trans isomers of 4 tert butyl cyclohexyl bromide... 

The E2 mechanism is a concerted process m which the carbon-hydrogen and carbon-halogen bonds both break m the same elementary step What if these bonds break m separate steps s... 

The best examples of El eliminations are those carried out m the absence of added base In the example cited m Eigure 5 12 the base that abstracts the proton from the car bocation intermediate is a very weak one it is a molecule of the solvent ethyl alcohol At even modest concentrations of strong base elimination by the E2 mechanism is much faster than El elimination... 

Like alcohol dehydrations El reactions of alkyl halides can be accompanied by carbocation rearrangements Eliminations by the E2 mechanism on the other hand nor mally proceed without rearrangement Consequently if one wishes to prepare an alkene from an alkyl halide conditions favorable to E2 elimination should be chosen In prac tice this simply means carrying out the reaction m the presence of a strong base... 

Section 5 16 The preceding equation shows the proton H and the halogen X m the anti coplanar relationship that is required for elimination by the E2 mechanism... 

Benzylic halides that are secondary resemble secondary alkyl halides in that they undergo substitution only when the nucleophile is weakly basic If the nucleophile is a strong base such as sodium ethoxide elimination by the E2 mechanism is faster than substitution... 

As depicted, the E2 mechanism involves a bimolecular transition state in which removal of a proton to the leaving group is concerted with departure of the leaving group. In contrast, the rate-determining step in the El mechanism is the unimolecular ionization of... 

A second piece of evidence in support of the E2 mechanism is provided by a phenomenon known as the deuterium isotope effect. For reasons that we won t go into, a carbon-hydrogen bond is weaker by about 5 kj/mol (1.2 kcal/mol) than the corresponding carbon-rfaiiferiwm bond. Thus, a C-H bond is more easily broken than an equivalent C-D bond, and the rate of C-H bond cleavage is faster. For instance, the base-induced elimination of HBv from l-bromo-2-phenylethane proceeds 7.11 times as fast as the corresponding... 

This mechanism, called the AdnS mechanism (termolecular addition, lUPAC AnAe)," has the disadvantage that three molecules must come together in the transition state. However, it is the reverse of the E2 mechanism for elimination, for which the transition state is known to possess this geometry (p. 1300). 

In the E2 mechanism (elimination, bimolecular), the two groups depart simultaneously, with the proton being pulled off by a base ... 

Among the evidence for the existence of the E2 mechanism are (1) the reaction displays the proper second-order kinetics (2) when the hydrogen is replaced by deuterium in second-order eliminations, there is an isotope effect of from 3 to 8, consistent with breaking of this bond in the rate-determining step. However, neither of these results alone could prove an E2 mechanism, since both are compatible with other mechanisms also (e.g., see ElcB p. 1308). The most compelling evidence for the E2 mechanism is found in stereochemical smdies. As will be illustrated in the examples below, the E2 mechanism is stereospecific the five atoms involved (including the base) in the transition state must be in one plane. There are two ways for this to happen. The H and X may be trans to one another (A) with a dihedral angle... 

We can conclude that anti elimination is generally favored in the E2 mechanism, but that steric (inability to form the anti-periplanar transition state), conformational, ion pairing, and other factors cause syn elimination to intervene (and even predominate) in some cases. 

The lUPAC designation is Dn + De (or Dn+Dh). This mechanism normally operates without an added base. Just as the E2 mechanism is analogous to and competes with the Sn2, so is the El mechanism related to the SnE In fact, the first step of the El is exactly the same as that of the SnI mechanism. The second step differs in that the solvent pulls a proton from the P carbon of the carbocation rather than attacking it at the positively charged carbon, as in the SnI process. In a pure El reaction (i.e., without ion pairs), the product should be completely nonstereospecific, since the carbocation is free to adopt its most stable conformation before giving up the proton. 

In the El mechanism, X leaves first, and then H. In the E2 mechanism, the two groups leave at the same time. There is a third possibility the H leaves first, and then the X. This is a two-step process, called the ElcB mechanism, or the carbanion mechanism, since the intermediate is a carbanion ... 

As in the E2 mechanism, it is not necessary that the C—H and C—X bond be equally broken in the transition state. In fact, there is also a spectrum of mechanisms here, ranging from a mechanism in which C—X bond breaking is a good deal more advanced than C—H bond breaking to one in which the extent of bond breaking is virtually identical for the two bonds. Evidence for the existence of the Ei mechanism is... 

The obvious way to distinguish between this mechanism and the ordinary E2 mechanism is by the use of deuterium labeling. For example, if the reaction is carried out on a quaternary hydroxide deuterated on the P carbon (R2CDCH2NMe OH ), the fate of the deuterium indicates the mechanism. If the E2 mechanism is in operation, the trimethylamine produced would contain no deuterium (which would be found only in the water). But if the mechanism is Ei, the amine would contain deuterium. In the case of the highly hindered compound (Me3C)2CDCH2NMe OH , the deuterium did appear in the amine, demonstrating an Ei mechanism for this ca.se. With simpler compounds, the mechanism is E2, since here the amine was deuterium-free. 

The mechanism of these reactions is often El. However, in at least some cases, an E2 mechanism operates.It has been shown that stereoisomers of cyclic y-amino halides and tosylates in which the two leaving groups can assume an anti-periplanar conformation react by the E2 mechanism, while those isomers in which the groups cannot assume such a conformation either fragment by the El mechanism or do not undergo fragmentation at all, but in either case give rise to side products characteristic of carbocations. " ... 

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