Acid-catalyzed dehydration of alcohols

Alcohols undergo acid-catalyzed dehydration reactions to form alkcnes. The reaction is accomplished by the formation of a carbocation intermediate. Thus there is the possibility of rearrangement in the process. First, we will take a look at the mechanism of this reaction. 

Predict the major product formed when the following compound is subjected to dehydrochlorination with sodium ethoxide in ethanol. H3C 

STRATEGY AND ANSWER We know that for an E2 dehydrochlorination to take place the chlorine will have to be axial. The following conformation has the chlorine axial and has two hydrogen atoms that are anti coplanar to the chlorine. Two products will be formed but (b) being more stable should be the major product. 

When di-l-bromo-4-tert-butylcyclohexane is treated with sodium ethoxide in ethanol, it reacts rapidly the product is 4-tcrt-butylcyclohexene. Under the same conditions, trans-l-bromo-4-tert-butylcyclohexane reacts very slowly. Write conformational structures and explain the difference in reactivity of these cis-trans isomers. 

The reaction is an elimination and is favored at higher temperatures (Section 6.18A). The most commonly used acids in the laboratory are Brpnsted acids— proton donors such as sulfuric acid and phosphoric acid. Lewis acids such as alumina (AI2O3) are often used in industrial, gas-phase dehydrations. 

The temperature and concentration of acid required to dehydrate an alcohol depend on the structure of the alcohol substrate. 

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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... 

As a method for the preparation of alkenes a weakness in the acid catalyzed dehydration of alcohols IS that the initially formed alkene (or mixture of alkenes) sometimes isomenzes under the conditions of its formation Write a stepwise mechanism showing how 2 methyl 1 butene might isomenze to 2 methyl 2 butene in the presence of sulfuric acid... 

We have seen this situation before m the reaction of alcohols with hydrogen halides (8ection 4 11) m the acid catalyzed dehydration of alcohols (8ection 5 12) and m the conversion of alkyl halides to alkenes by the El mechanism (8ection 5 17) As m these other reactions an electronic effect specifically the stabilization of the carbocation intermediate by alkyl substituents is the decisive factor The more stable the carbo cation the faster it is formed... 

Diethyl ether and other simple symmetrical ethers are prepared industrially by the sulfuric acid-catalyzed dehydration of alcohols. The reaction occurs by SN2 displacement of water from a protonated ethanol molecule by the oxygen atom of a second ethanol. Unfortunately, the method is limited to use with primary alcohols because secondary and tertiary alcohols dehydrate by an El mechanism to yield alkenes (Section 17.6). 

Dehydrations produce olehns from alcohols by the acid-catalyzed elimination of a water molecule from between two carbons. Acid-catalyzed dehydrations often give mixtures of products because the intermediate carbocation is prone to cationic rearrangements to more stable carbocations prior to formation of the olefin product. Moreover, even when the intermediate carbocation is not subject to skeletal rearrangement, as in file case of tertiary alcohols, mixtures of regioisomers are often produced during file loss of a proton from file carbocation. As a consequence, the acid-catalyzed dehydration of alcohols is generally not a viable synthetic method. 

Surprisingly, the kinetic measurements now available for the nucleophilic trapping of carbocations with water are not always matched by measurements of rate constants for formation of the carbocation from the corresponding alcohol required to evaluate the equilibrium constant AR. Although carbocations are reactive intermediates in the acid-catalyzed dehydration of alcohols to form alkenes,85,86 the equilibrium in this reaction usually favors the alcohol and the carbocation forming step is not rate-determining. Rate constants may... 

In writing mechanisms for acid-catalyzed dehydration of alcohols, begin with formation of the carbocation intermediate ... 

Alcohols and phenols are also weak bases. They can be protonated on the oxygen by strong acids. This reaction is the first step in the acid-catalyzed dehydration of alcohols to alkenes and in the conversion of alcohols to alkyl halides by reaction with hydrogen halides. Alkyl halides can also be prepared from alcohols to alkyl halides by reaction with hydrogen halides. Alkyl halides can also be prepared from alcohols by reaction with thionyl chloride or phosphorus halides. 

Treatment of an alkene with a strong acid, such as sulfuric acid, that has a relatively nonnucleophilic conjugate base results in the addition of the elements of water (H and OH) to the double bond. This reaction has many similarities to the addition of the halogen acids described in Section 11.2. First H+ adds to produce a carbocation and then water acts as the nucleophile. The reaction follows Markovnikov s rule and the stereochemistry is that expected for a reaction that involves a carbocation—loss of stereochemistry. Some examples are provided in the following equations. Note that the mechanism is the exact reverse of the El mechanism for acid-catalyzed dehydration of alcohols described in Section 10.13. 

This chapter has focused on heterogeneous catalysis in supercritical media, but the relationship between supercritical fluids and catalysis is much broader. There have been numerous studies of homogeneous catalysis in SCFs. Examples include hydroformylation via cobalt carbonyl complexes in supercritical CO2, oxidation via metal salts dissolved in supercritical water, and acid-catalyzed dehydration of alcohols in supercritical water. 

Symmetrical ethers can be synthesized by acid-catalyzed dehydration of alcohols. 

Evidence lor the intemiediate carbocatiom in the acid-catalyzed dehydration of alcohols comes from the observation that rearrangements sometimes occur. Propose a mechanism to account for the formation ol 2.3-dimethyl-2-bulene from 3,3-dimethyl-2-butanol. ... 

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... 

Ramayya S. Brittain A. DeAlmeida C. Mok W.S. Antal M.J, Jr, (1987) Acid-catalyzed dehydration of alcohols in supercritical water. Fuel 66, 1364-1371. 

Problem 21.9 (a) In the acid-catalyzed dehydration of alcohols (Sec. 5.20), what is the base involved (b) In the base-catalyzed racemization and hydrogen exchange of phenyl jec-butyl ketone (Problem 21.5, p. 707), what is the acid involved ... 

There is a strong similarity between the mechanism shown in Figure 5.12 and the one shown for alcohol dehydration in Figure 5.6. Indeed, we can describe the acid-catalyzed dehydration of alcohols as an El elimination of their conjugate acids. The main difference between the dehydration of 2-methyl-2-butanol and the dehydrohalogenation of 2-bromo-2-methylbutane is the source of the carbocation. When the alcohol is the substrate, it is the corresponding alkyloxonium ion that dissociates to form the carbocation. The alkyl halide ionizes directly to the carbocation. 

Applicability of High-Temperature Water. At first glance, an aqueous environment would not seem a useful medium for conducting dehydrations, such as those observed here for the terpenols and P-ionone. However, dehydration reactions in high-temperature water are not novel, with the conversion of cyclohexanol to cyclohexene having been recently investigated by Kuhlmann et al. (20). Acid catalyzed dehydrations of alcohols usually proceed by El mechanisms, via carbocation intermediates (24-26), so the product distributions obtained here from the monoterpenoids in high temperature water were not unexpected. 

R can be aryl and/or alkyl. Ethers can be formed by two alcohols molcules in the presence of strong acid to release a water molecule. This is called acid-catalyzed dehydration of alcohols to form ethers. 

As mentioned earlier, the first step of an acid-catalyzed dehydration of alcohol is the protonation of the alcohol. The elimination of a water molecule to form the carbonium ion from the protonated alcohol is the slowest step. Therefore, it is the rate-limiting step. 

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