Primary alcohols acid-catalyzed dehydration

The reaction is an F.1 process and occurs through the three-step mechanism shown in Figure 17.6). As usual for El reactions (Section 11.10), only tertiary alcohols are readily dehydrated with acid. Secondary alcohols can be made to react, but the conditions are severe (75% H2S04,100 °C) and sensitive molecules don t survive. Primary alcohols are even less reactive than secondary ones, and very harsh conditions are necessary to cause dehydration (95% H2S04,150 °C). Thus, the reactivity order for acid-catalyzed dehydrations is... 

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). 

The primary alcohol initially undergoes acid-catalyzed dehydration by an E2 mechanism... 

Symmetric ethers (R = R ) can be prepared by the acid-catalyzed dehydration of primary alcohols. However, this reaction competes with the acid-catalyzed dehydration of the alcohol to form an alkene. Lower temperatures favor ether formation over alkene formation. Secondary and tertiary alcohols favor alkene formation. The general reaction is shown in Figure 3-29. 

The characteristic reaction of an alcohol on being heated with KHS04 is acid-catalyzed dehydration. Secondary alcohols dehydrate faster than primary alcohols, and so a reasonable first step is... 

Hydride Reduction of a Carbonyl Group 454 Reaction of a Tertiary Alcohol with HBr(S[ 1) 480 Reaction of a Primary Alcohol with HBr (SN2) 480 Reaction of Alcohols with PBr3 485 (Review) Acid-Catalyzed Dehydration of an Alcohol 487 The Pinacol Rearrangement 495 Cleavage of an Ether by HBr or HI 639 Acid-Catalyzed Opening of Epoxides in Water 649 Acid-Catalyzed Opening of an Epoxide in an Alcohol Solution 650... 

As noted earlier (Section 4.10) primary carbocations are too high in energy to be intermediates in most chemical reactions. If primary alcohols don t form primary carbocations, then how do they undergo elimination A modification of our general mechanism for alcohol dehydration offers a reasonable explanation. For primary alcohols it is believed that a proton is lost from the alkyloxonium ion in the same step in which carbon-oxygen bond cleavage takes place. For example, the rate-determining step in the sulfuric acid-catalyzed dehydration of ethanol may be represented as ... 

The least expensive method for synthesizing simple symmetrical ethers is the acid-catalyzed bimolecular dehydration, discussed in Section 11-IOB. Unimolecular dehydration (to give an alkene) competes with bimolecular dehydration. To form an ether, the alcohol must have an unhindered primary alkyl group, and the temperature must be kept low. If the alcohol is hindered or the temperature is too high, the delicate balance between substitution and elimination shifts in favor of elimination, and very little ether is formed. Bimolecular dehydration is used in industry to make symmetrical ethers from primary alcohols. Because the dehydration is so limited in its scope, it finds little use in the laboratory synthesis of ethers. 

An alcohol can be converted to an alkene by dehydration—that is, by the elimination of a molecule of water from adjacent carbon atoms. In the laboratory, the dehydration of an alcohol is most often brought about by heating it with either 85% phosphoric acid or concentrated sulfuric acid. Primary alcohols are the most difficult to dehydrate and generally require heating in concentrated sulfuric acid at temperatures as high as 180 °C. Secondary alcohols undergo acid-catalyzed dehydration at somewhat lower temperatures. The... 

Another study pertinent to the present discussion is that of the acid-catalyzed dehydration of tetratols, pentitols, and hexitols, all of which yield tetrahydrofuran derivatives as the primary products. These reactions are first order with respect to the alcohol and the acidity function Hq, and the direct relationship shown from plots of versus Hq implies that the reaction proceeds via a protonated intermediate.In all cases except one, the major cyclic product is derived from HO-5 displacement of water from C-1. The exception is D-mannitol (213), where HO-3 participation leads to a slight preference for formation of 2,5-anhydro-D-glucitol (214) over 1,4-anhydro-D-mannitol (215). Inversion at C-2 occurs with HO-5 participation during ring opening of the epoxide (214). 

Acid-Catalyzed Dehydration of an Unbranched Primary Alcohol (Section 10.6)... 

Dehydration of primary and secondary alcohols is often accompanied by rearrangement. Acid-catalyzed dehydration of 3,3-dimethyl-2-butanol, for example, gives a mixture of two alkenes, each of which is the result of a rearrangement. 

Based on the relative rates of dehydration of alcohols (3° > 2° > 1°) and the prevalence of rearrangement, particularly among primary and secondary alcohols, chemists propose a three-step mechanism for acid-catalyzed dehydration of secondary and tertiary alcohols. This mechanism involves formation of a carbocation in the rate-determining step and therefore is classified as an El mechanism. 

Primary alcohols with little or no S-branching undergo acid-catalyzed dehydration to give a terminal alkene and rearranged alkenes. Acid-catalyzed dehydration of 1-butanol, for example, gives only 12% of 1-butene. The major product is a mixture of the trans and cis isomers of 2-butene. 

Diethyl ether and several other commercially available ethers are synthesized on an industrial scale by the acid-catalyzed dehydration of primary alcohols. Intermolecular dehydration of ethanol, for example, gives diethyl ether. 

Yields of ethers from the acid-catalyzed intermolecular dehydration of alcohols are highest for symmetrical ethers formed from unbranched primary alcohols. Examples of symmetrical ethers formed in good yield by this method are dimethyl ether, diethyl ether, and dibutyl ether. From secondary alcohols, yields of ether are lower because of competition from acid-catalyzed dehydration (Section 10.6). In the case of tertiary alcohols, dehydration to an alkene is the only reaction. 

Acid-Catalyzed Dehydration of Alcohols (Section 11.4B) Yields are highest for symmetrical ethers formed from unbranched primary alcohols. The mechanism involves protonation of an —OH group followed by displacement of the HjO leaving group by a second alcohol molecule acting as a nucleophile followed by loss of a proton to give the ether. 

We have seen a similar trend in the reaction of alcohols with hydrogen halides (Section 4.10), in the acid-catalyzed dehydration of alcohols (Section 5.12), and in the conversion of alkyl halides to alkenes by the El mechanism (Section 5.18). As in these other reactions, the more stable the carbocation, the faster it is formed, and the faster the reaction rate. Methyl and primary carbo-cations are so high in energy that they are unlikely intermediates in nucleophilic substitutions. Although methyl and ethyl bromide undergo hydrolysis under the condirions just described, substitution probably takes place by an Sn2 process in which water is the nucleophile. 

Alcohols react with alkylating and acylating agents they ako react with other electrophiles e.g., primary and secondary alcohols may be oxidized, and tertiary alcohols are especially susceptible to acid-catalyzed dehydration. It is therefore often necessary to protect alcoholic hydroxyl groups if it is intended to effect a chemical reaction solely at another site in a molecule. Such protection ako prevents the possibility of neighbouring group participation by hydroxyl groups. 

The acid-catalyzed or thermal elimination of water from alcohols is a favorite laboratory method for the preparation of olefins. Isomeric mixtures usually arise with the acid-catalyzed method. The order of reactivity in dehydration usually follows the order of stability of the intermediate (transient) carbonium ion, i.e., tertiary > secondary > primary. The acid-catalyzed procedure is illustrated below, where a 79-87% yield of cyclohexene is obtained [1-3]. 

An example of a conventional cascade system with two catalysts comprising a high-valent metal triflate Lewis add and a supported Pd catalyst for the hydrogenolysis of ethers is illustrated in Fig. 8.24. Since primary C—O bonds are resistant to cleavage, in the presence of water, there is formation of the parent primary alcohol that further undergoes acid-catalyzed dehydration to alkene and rapid, irreversible metal-catalyzed hydrogenation to alkane. 

In general, the acid catalyzed esterification of organic acids can be accomplished easily with primary or secondary alkyl or aryl alcohols, but tertiary alcohols usually give carbonium ions which lead to dehydration. The structure of the acid is also of importance. As a rule, the more hindered the acid is alpha to the carbonyl carbon the more difficult esterification becomes (20A). 

It was recently shown by Zhang and coworkers that Ru(PPh3)3Cl2 is a suitable catalyst for the alkylative coupling of tertiary alcohols 186 to primary alcohols 185 leading to branched alcohols 187 in 32-98% yield (Fig. 46) [258]. The reaction required the presence of a Lewis acid, such as BF3 OEt2. It mediates the dehydration of the tertiary alcohol to a 1,1-disubstituted alkene, which coordinates the ruthenium catalyst. The further course is likely to be similar to the corresponding iron- or rhodium-catalyzed reactions (see Sects. 2.8 and 6). 

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