Acid-Catalyzed Ring Opening of Epoxides

Epoxides are much more reactive than common dialkyl ethers because of the large strain energy (about 105 kJ/mol or 25 kcal/mol) associated with the three-membered ring. Unlike other ethers, epoxides react under both acidic and basic conditions. The products of acid-catalyzed opening depend primarily on the solvent used. 

In Water In Section 8-13 we saw that acid-catalyzed hydrolysis of epoxides gives glycols with anti stereochemistry. The mechanism of this hydrolysis involves protonation of oxygen (forming a good leaving group), followed by 8 2 attack by 

Direct anti hydroxylation of an alkene (without isolation of the epoxide intermediate) is possible by using an acidic aqueous solution of a peroxyacid. As soon as the epoxide is formed, it hydrolyzes to the glycol. Peroxyacetic acid (CH3CO3H) and peroxyformic acid (HCO3H) are often used for the anti hydroxylation of alkenes. 

Propose mechanisms for the epoxidation and ring-opening steps of the epoxidation and hydrolysis of lr ns-2-butene shown above. Predict the product of the same reaction with cis-2 butene. 

In Alcohols When the acid-catalyzed opening of an epoxide takes place with an alcohol as the solvent, a molecule of alcohol acts as the nucleophile. This reaction produces an alkoxy alcohol with anti stereochemistry. This is an excellent method for making compounds with ether and alcohol functional groups on adjacent carbon atoms. For example, the acid-catalyzed opening of 1,2-epoxycyclopentane in a methanol solution gives trans-2-methoxycyclopentanol. 

The reaction of Grignard reagents with epoxides is regioselective in the same sense. Attack occurs at the less substituted carbon of the ring. 

Epoxides are reduced to alcohols on treatment with lithium aluminum hydride. Hydride is transferred to the less substituted carbon. 

Epoxidation of an alkene, followed by lithium aluminum hydride reduction of the resulting epoxide, gives the same alcohol as would be obtained by hydration (Section 6,9) of an alkene in accordance with Markovnikov s rule. 

As we ve just seen, nucleophilic ring opening of ethylene oxide yields 2-substituted derivatives of ethanol. Those reactions involved nucleophilic attack on the carbon of the ring under neutral or basic conditions. Other nucleophilic ring openings of epoxides likewise give 2-substituted derivatives of ethanol but involve an acid as either a reactant or a catalyst. 

A third example is the industrial preparation of ethylene glycol (HOCH2CH2OH) by hydrolysis of ethylene oxide in dilute sulfuric acid. This reaction and its mechanism (Mechanism 16.3) illustrate the difference between the ring openings of ethylene oxide discussed in the preceding section and the acid-catalyzed ones described here. In acid, the species that is attacked by the nucleophile is not the epoxide itself, but rather its 

Nucleophilic ring openings of epoxides can be catalyzed by acids. 

There is an important difference in the regioselectivity of ring-opening reactions of epoxides in acid solution compared with their counterparts in base. Unsymmetrically substituted epoxides tend to react with anionic nucleophiles at the less hindered carbon of the ring. Under acid-catalyzed conditions, however, reaction occurs at the more substituted carbon. 

Nucleophiles attack here when reaction is acid-catalyzed. 

As seen in Mechanism 16.3, the reaction just described involves three steps. Steps 1 and 3 are proton transfers step 2 involves methanol acting as a nucleophile toward the protonated epoxide. The transition state for this step has a fair amount of carbocation character breaking the C—O bond of the ring is more advanced than formation of the bond to the nucleophile. 

Transition state for reaction of methanol with conjugate acid of 2,3-epoxy-2-methylbutane 

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Acid-catalyzed ring opening of epoxides is discussed in Section 16.13. 

Nichols and co-workersstudied the formation of j8-hydroxy nitrate esters via the acid-catalyzed ring-opening of epoxides with nitrate anion. Reactions were conducted in aqueous media using solutions of ammonium nitrate is nitric acid and under nonaqueous conditions using solutions of pure nitric acid in chloroform. 2-Nitratoethanol (32) is formed in 58 % yield from ethylene oxide (30) using either of these methods. ... 

The ethylene glycol, bp 198°C, is readily vacuum distilled and separated from the DEG, bp 246°C, and TEG, bp 288°C. The mechanism of the reaction follows the general scheme for acid-catalyzed ring openings of epoxides. 

Summary Epoxide Syntheses 648 14-12 Acid-Catalyzed Ring Opening of Epoxides 649... 

The acid-catalyzed ring opening of epoxides shows a stereoselectivity typical of 8 2 reactions The nucleophile attacks anti to the leaving hydroxyl group, and the —OH groups in the glycol thus formed are anti. As a result, the acid[Pg.266]

We have presented carbocation rearrangements in the context of substitution reactions. Yet, rearrangements and issues that are relevant to carbocation structure are applicable to any reaction involving carbocations—namely, additions, eliminations, rearrangements, etc. One example is the acid-catalyzed ring opening of epoxides. 

The degree of epoxidation can be controlled by the stoichiometric addition of percarboxylic acids [124-126]. When aiming for high epoxidation levels in the polymer, the quantity of peracid needs to be increased over a 1 1 molar ratio. The concomitant high concentration of carboxylic acids in the reaction media leads to side reactions [99, 118, 124] an acid-catalyzed ring opening of epoxides by water or the carboxylic acid can occur. The resulting PBD contains vicinal hydroxyl... 

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