The El and E2 Mechanisms of Alcohol Dehydration

The dehydration of alcohols resembles the reaction of alcohols with hydrogen halides (Section 4.7) in two important ways. 

The relative reactivity of alcohols increases in the order primary secondary tertiary. 

These common features suggest that carbocations are key intermediates in alcohol dehydrations, just as they are in the reaction of alcohols with hydrogen halides. Mechanism 5.1 portrays a three-step process for the acid-catalyzed dehydration of tert-h xiy alcohol. Steps 1 and 2 describe the generation of tert-h xiy cation by a process similar to that which led to its formation as an intermediate in the reaction of tert-b xiy alcohol with hydrogen chloride. 

Like the reaction of tert-h xiy alcohol with hydrogen chloride, step 2 in which r -butyloxonium ion dissociates to (CH3)3C and water, is rate-determining. Because the rate-determining step is unimolecular, the overall dehydration process is referred to as a unimolecular elimination and given the symbol El. 

Step 3 is an acid-base reaction in which the carbocation acts as a Brpnsted acid, transferring a proton to a Brpnsted base (water). This is the property of carbocations that is of the most significance to elimination reactions. Carbocations are strong acids they are the conjugate acids of alkenes and readily lose a proton to form alkenes. Even weak bases such as water are sufficiently basic to abstract a proton from a carbocation. 

Each of the following alcohols has been subjected to acid-catalyzed dehydration and yields a mixture of two isomeric alkenes. Identify the two alkenes in each case, and predict which one is the major product on the basis of the Zaitsev rule. 

Sample Solution (a) Dehydration of 2,3-dimethyl-2-butanol can lead to either 2,3-dimethyl-l-butene by removal ot a C-1 hydrogen or to 2,3-dimethyl-2-butene by removal of a C-3 hydrogen. 

The major product is 2,3-dimethyl-2-butene. It has a tetrasubstituted double bond and is more stable than 2,3-dimethyl-l-butene, which has a disubstituted double bond. The major alkene arises by loss of a hydrc en from the P carbon that has fewer attached hydrc ens (C-3) rather than from the p carbon that has the greater number of hydrogens (C-1). 

In addition to being regioselective, alcohol dehydrations are stereoselective. A stereoselective reaction is one in which a single starting material can yield two or more ster-eoisomeric products, but gives one of them in greater amounts than any other. Alcohol dehydrations tend to produce the more stable stereoisomer of an alkene. Dehydration of 3-pentanol, for example, yields a mixture of fran5 -2-pentene and c 5 -2-pentene in which the more stable trans stereoisomer predominates. 

What three alkenes are formed in the acid-catalyzed dehydration of 2-pentanol  

---

Pines and Manassen [7] suggested that tertiary alcohols are dehydrated by the El mechanism involving the formation of more or less free car-bonium ions, secondary alcohols by a mechanism lying somewhere between El and E2 (i.e. synchronous with a ionic contribution) and primary alcohols by a concerted E2 mechanism. However, the large kinetic isotope effect for the dehydration of fully deuterated tert-butanol on alumina [122] indicates that, even in this case, some synchrony must exist. Alumina strongly prefers the concerted process and with other catalysts the situation may differ. 

The above categories are rarely clear cut and quite often an intermediate situation can occur, particularly with El and E2 pathways. The nature of the alcohol is of importance and the order of ease of dehydration is tertiary > secondary > primary and tertiary alcohols tend to react via an El mechanism because of the relative stability of the tertiary carbonium ion. 

Mechanistic Studies of Alcohol Dehydration on Zeolites. - Gentry and Rudham and Jacobs et al have proposed mechanisms for the dehydration of propan-2-ol and butan-2-ol on X-zeolites. Both groups of workers are in basic agreement about the mechanism, which involves the formation of oxonium and carbonium ions. The formation of olefins from the above alcohols appeared to occur via an El -like mechanism and this was supported very strongly by the behaviour of butan-2-ol, which gave a primary isotope effect, but an absence of one for C 3- H, rules out the E2 mechanism. 

List two of the major differences in the dehydration of an alcohol by an El and E2 reaction mechanism. 

In Chapter 9, we saw that we can prepare alkenes by dehydrohalogenation. The dehydration of alcohols also gives alkenes, but this reaction occurs with rearrangement of the carbocation, and gives mixtures of products having different carbon skeletons. The elimination of a hydrogen hahde from an alkyl halide is a complex process. We must consider both rcgiochemistry and stereoelectronic effects. These effects are related to the mechanism of the reaction, which may be either E2 or El. 

Dehydration of p-hydroxyketones is both a common reaction (we will see in Chapters 17 and 20 why these molecules are easy to prepare) and a very straightforward one. The product obtained is invariably the conjugated one, whatever the mechanism. Acid-catalyzed reactions are common they are usually El with tertiary alcohols and E2 with primary alcohols. Secondary alcohols such as 10.18 may react by either or both mechanisms. 

Dehydration of alcohols (Sections 5 9-5 13) Dehydra tion requires an acid catalyst the order of reactivity of alcohols IS tertiary > secondary > primary Elimi nation is regioselective and proceeds in the direction that produces the most highly substituted double bond When stereoisomeric alkenes are possible the more stable one is formed in greater amounts An El (elimination unimolecular) mechanism via a carbo cation intermediate is followed with secondary and tertiary alcohols Primary alcohols react by an E2 (elimination bimolecular) mechanism Sometimes elimination is accompanied by rearrangement... 

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. 

These relations seem to be valid for the dehydration of primary alcohols, but secondary and tertiary alcohols may need other combinations of acidic and basic sites. It has been observed that the dehydration of tert-butanol was more sensitive to the presence of strongly acidic sites than the reaction of methanol, but both processes required basic sites [8]. All this is in accordance with the dynamic model of elimination mechanisms presented in Sect. 2.1, which allows transition from El to E2 or further to ElcB according to the structure of the reactant and the nature of the catalyst. 

The mechanism of dehydration depends on the structure of the alcohol 2° and 3° alcohols react by an El mechanism, whereas 1° alcohols react by an E2 mechanism. Regardless of the type of alcohol, however, strong acid is always needed to protonate the O atom to form a good leaving group. 

The acid-catalyzed dehydration of alcohols with H2SO4 or TsOH yields alkenes, too (Sections 9.8 and 9.9). The reaction occurs via an El mechanism for 2° and 3° alcohols, and an E2... 

The mechanism by which proton acids catalyze the dehydration of primary and secondary alcohols in water is not perfectly well understood (1). There is universal agreement that the dehydration of tertiary alcohols can be explained by an El mechanism (1,2) involving either a II complex ( ) or a symmetrically solvated carbonium ion (4) as the key reaction intermediate. Although an occasional text ( ) also describes the dehydration of primary alcohols by an El mechanism, authoritative reviews (1/4) conclude that a concerted E2 type mechanism is more probable. The dehydration behavior of secondary alcohols is presumed to be similar to primary alcohols (4). Discussions of the gas phase dehydration of alcohols by heterogeneous Lewis acid catalysts admit more possibilities. In their authoritative review Kut, et al. (1) consider E1-, E2-, and ElcB-like mechanisms, as well as the possible role of diethyl ether as a reaction intermediate, but they reach no conclusion concerning the relative importance of these mechanisms in the formation of olefins from alcohols. 

Dehydration of primary alcohols apparently proceeds through an E2 mechanism because the primary carbocation required for dehydration by an El mechanism is relatively unstable. The first step in dehydration of a primary alcohol is protonation, just as in the El mechanism. Then, with the protonated hydroxyl as a good leaving group, a Lewis base in the reaction mixture removes a j8 hydrogen simultaneously with formation of the alkene double bond and departure of the protonated hydroxyl group (water). 

Tertiary and secondary alcohols undergo add-catalyxed dehydration by an El mechanism primary alcohols are dehydrated by an E2 mechanism. In either mechanism, the first step is the rapid protonation of the lone pair electrons of the oxygen atom to produce an allqfloxonium ion. The acid is represented as HA in the reaction mechanism for the dehydration of tert-huty alcohol shown below. 

Elimination reactions of primary alcohols occurs by an E2 mechanism in an acid-cataly2ed reaction. First, the acid protonates the oxygen of a primary alcohol to give a primary alkyl oxonium ion. Then, water is lost by an E2 mechanism because a primary carbocation is too unstable to form in an El process. This concerted step resembles the reaction of primary alkyl hahdes with a base. The proton of the alkyl oxonium ion is deprotonated by a Lewis base, which is water in the dehydration of alcohols. The electron pair in the C—H bond moves to form a carbon-carbon double bond, and the electron pair of the C—O bond is retained by the oxygen atom. The reaction with ethanol illustrates the process. In both the El process and the E2 dehydration reaction, the acid serves only as a catalyst. It is regenerated in the last step of the reaction. 

In Section 6.4, we saw that 1,2 hydtide shifts occur in the carbocations formed in addition reactions. We have also seen that 1,2-hydtide shifts can also occur in carbocations that are generated in dehydration reactions if a more stable carbocation results. Such 1,2-hydtide shifts occur even in the dehydration of primary alcohols. For example, the dehydration of 1-decanol gives 1-decene as a minor product, which may result from an E2 mechanism. However, the major product is largely a mixture of cis- and rw r-2-decenes. This product could result from loss of a proton by an El mechanism from a secondary carbocation formed by a hydride shift of a primary carbocation. 

Siddan and Narayan also employed 7-AI2O3 and Th02 for the dehydration of a number of model alcohols and observed that if the basicity of the alumina was increased by Na -ion doping, 7-elimination was enhanced using both neopentyl and pinacolyl alcohol. It appeared that as the alumina became less acidic and more basic, there was a shift from El/E2-like behaviour to an ElcB-type mechanism, which manifested itself in a concerted 7-elimination (Scheme 10 for neopentyl alcohol A,B = acid, base sites respectively reproduced by permission from J. Catal, 1979, 59, 405). This tendency was also observed by use of erythrof f/ireo)-3-methylpentan-2-ol. 

---