Elimination by the E2 and Elcb Mechanisms

C(sp3)-X electrophiles can undergo / elimination reactions as well as substitutions. / -Elimination reactions proceed by the E2 or Elcb mechanism under basic conditions. The concerted E2 mechanism is more common. The lone pair of the base moves to form a bond to a H atom on a C atom adjacent to the electrophilic C atom. The electrons in the H-C bond simultaneously move to form a 7r bond to the electrophilic C atom. Because this C atom already has its octet 

In cyclic compounds, there are much greater restrictions on conformational flexibility. In six-membered rings, the antiperiplanar requirement for E2 elimination is satisfied when both the leaving group and the adjacent H atom are axial. Compounds in which such a conformation is readily achievable undergo E2 elimination much more readily than those in which it is not. For example, in menthyl chloride, the C-Cl bond is not antiperiplanar to any adjacent C-H bond in the lowest energy conformation, and E2 elimination is therefore much slower than it is in the diastereomer neomenthyl chloride, in which the C-Cl bond is antiperiplanar to two C-H bonds in the lowest energy conformation. Moreover, two C-H bonds are antiperiplanar to the C-Cl bond in the reactive conformation of neomenthyl chloride, so two products are obtained upon E2 elimination, whereas only one C-H bond is antiperiplanar to the C-Cl bond in the reactive conformation of menthyl chloride, so only one product is obtained. 

Not only can 1° and 2° C(sp3)-X undergo /3-elimination by the E2 mechanism under basic conditions, but so can 3° C(sp3)-X systems. Alkenyl halides also undergo /5-el i mi nation readily. When there are H atoms on either side of an alkenyl halide, either an alkyne or an allene may be obtained. Even alkenyl ethers (enol ethers) can undergo /3-elimination to give an alkyne. 

E2 eliminations, in which a tt bond is interposed between the two C atoms at which bond breaking occurs, are also seen. In the following example, the base is F, and a Me3Si group replaces the usual H. 

When the H is particularly acidic (usually because it is adjacent to a carbonyl) and the leaving group is particularly poor (especially OH and OR), a two-step mechanism called Elcb operates. In this mechanism, the acidic proton is removed first to make a stabilized carbanion. Then the lone pair on C moves to make a ir bond to the neighboring electrophilic C atom, expelling the leaving group. The dehydration of an aldol (/3-hydroxycarbonyl compound) is the most common example of an elimination reaction that proceeds by the Elcb mechanism. 

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Substitution by the SN2 mechanism and -elimination by the E2 and Elcb mechanisms are not the only reactions that can occur at C(sp3)-X. Substitution can also occur at C(sp3)-X by the SRN1 mechanism, the elimination-addition mechanism, a one-electron transfer mechanism, and metal insertion and halogen-metal exchange reactions. An alkyl halide can also undergo a-elimination to give a carbene. 

The transition states of the E2 and ElcB mechanisms are represented in Fig. 37.3 together with the KIEs that should be observed in each case. Just by comparing the three transition states, it becomes clear that no primary D KIE should be observed in the (E1cB)r mechanism, as the proton has been already removed. As the experimental fact is a clear primary D KIE at C3, the EIcBr mechanism must be discarded. Additionally it is an experimental fact that no H/D exchange with the solvent has been observed in the elimination of substrates 1. Solvent H/D exchange is indicative for an EIcBr mechanism where the carbanion is reprotonated by the solvent in the fast initial step (see equation C in Scheme 37.2). 

The mechanistic borderline between E2 and ElcB mechanisms has been studied under various conditions.1,2 The mechanism of the elimination reaction of 2-(2-fluoroethyl)-1-methylpyridinium has been explored explored by Car-Parrinello molecular dynamics in aqueous solution.3 The results indicated that the reaction mechanism effectively evolves through the potential energy region of the carbanion the carbon-fluoride bond breaks only after the carbon-hydrogen bond. 

In the previous section, three general mechanisms of olefin formation by beta-elimination of the elements HX from adjacent carbon atoms, were outlined. Whereas the El and ElcB mechanisms involve preliminary breaking of one bond, the E2 process is concerted, both the C -H and C -X bonds being partially broken at the transition state. When initially designating... 

Effect of solvent on El vs. E2 vs. ElcB. With any reaction a more polar environment enhances the rate of mechanisms that involve ionic intermediates. For neutral leaving groups, it is expected that El and ElcB mechanisms will be aided by increasing polarity of solvent and by increasing ionic strength. With certain substrates, polar aprotic solvents promote elimination with weak bases (the E2C reaction). 

In trans-1 -bromo-2-fluorocyclohexane, E2 elimination occurs in the treatment of the compound with sodium methoxide or potassium tert-butoxide. There is only one hydrogen antiperiplanar to bromine, and its elimination leads to 3-fluorocyclohexene W. On the other hand, when, sodamide is used as a base, hydrogen fluoride is eliminated, not by the E2 mechanism but by a cA-elimination leading to X, 1-bromocyclohex-ene, probably by Elcb (carbanion) mechanism [132. ... 

Elimination reactions involve breaking a C—H bond and breaking a C—X bond. In principle, there are three modes by which the bond-breaking can take place (Table 2.3). In the first mode, the C—H bond breaks first to give an anionic intermediate, and then the C—X bond breaks. In the second mode, the two bonds break simultaneously. In the third mode, the C—X bond breaks to give a cationic intermediate, and then the C—H bond breaks. The Elcb and E2 mechanisms that occur under basic conditions take place by the first and second modes, respectively. The third mode generally does not take place under basic conditions, but under acidic conditions, where carbocations can exist, the third mode is quite common, and it is known as El. 

These reactions are often promoted by a strong base, which assists the departure of the proton. X is the leaving group. Both El and E2 mechanisms are known, as is a variant designated Elcb, for unimolecular elimination from the conjugate base of the substrate. ... 

All three elimination reactions--E2, El, and ElcB—occur in biological pathways, but the ElcB mechanism is particularly common. The substrate is usually an alcohol, and the H atom removed is usually adjacent to a carbonyl group, just as in laboratory reactions. Thus, 3-hydroxy carbonyl compounds are frequently converted to unsaturated carbonyl compounds by elimination reactions. A typical example occurs during the biosynthesis of fats when a 3-hydroxybutyryl thioester is dehydrated to the corresponding unsaturated (crotonyl) thioester. The base in this reaction is a histidine amino acid in the enzyme, and loss of the OH group is assisted by simultaneous protonation. 

The fact that the rate law of hydrogen bromide elimination is first order with respect to the base may be interpreted by an E2 mechanism. The antiperiplanar position of the hydrogen and the bromine atoms in Ih also makes this mechanism very likely. Earlier the same mechanism was proposed for the elimination reaction of some tertiary a-halo ketones (ref. 19). Other mechanism, such as ElcB or El, seems to be very improbable considering the lack of any deuteration at C-2 or the lack of any rearrangement and the fact that the generation of a-keto cations requires acidic conditions (ref. 20). 

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... 

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