Acid-Catalyzed Epoxide Hydrolysis

The acid-catalyzed ring openings of ethylenimine and 2-ethyl-ethylenimine have also been characterized as A-2 reactions (Earley et al., 1958). The entropies of activation are —9-4 and —10.0 e.u., respectively. However, AS for the reaction of 2,2-dimethylethylenimine is —1.9 e.u., suggesting incursion of the unimolecular mechanism, a conclusion which is supported on other grounds (Earley et al., 1958). The volume changes of activation have also been measured (Earley et al., 1958). These results, if interpreted in terms of Whalley s (1959) criterion, would indicate the A-l mechanism for ethylenimine and the A-2 for the ethyl and dimethyl derivatives, a conclusion which seems unacceptable. 

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Alkenes are reduced by addition of H2 in the presence of a catalyst such as platinum or palladium to yield alkanes, a process called catalytic hydrogenation. Alkenes are also oxidized by reaction with a peroxyacid to give epoxides, which can be converted into lTans-l,2-diols by acid-catalyzed epoxide hydrolysis. The corresponding cis-l,2-diols can be made directly from alkenes by hydroxylation with 0s04. Alkenes can also be cleaved to produce carbonyl compounds by reaction with ozone, followed by reduction with zinc metal. 

Several conclusions are drawn from the product studies of the reactions of propylene oxide and isobutylene oxide in H O.23 In the acid-catalyzed hydrolysis of propylene oxide, cleavage of the secondary C-O bond is favored by a factor of 2-3 over cleavage of the primary C-O bond. In the acid-catalyzed hydrolysis of isobutylene oxide, cleavage of the tertiary C-O bond is highly favored (>99%). These results show that in acid-catalyzed epoxide hydrolysis, cleavage of the C-O bond leading to... 

The acid-catalyzed hydrolysis of p-phenyl-substituted cyclohexene oxides 49a-d yields diols resulting from cis and "trans addition of water to the epoxide group (Scheme 14). It was initially reported that the cis/trans diol ratio correlates well with the electronic effect of the / -substituent, and varied from 7.5 93.5 for p-nitro-sub-stituted oxide 49d to 95.3 4.7 for p-methoxy-substituted epoxide 49a.56 58 Later work established that methoxy-substituted diols 50a and 51a underwent isomerization under the conditions of acid-catalyzed epoxide hydrolysis, and that the cis/ trans diol ratios for hydrolysis of 49a-c are quite similar.59... 

The interpretation of the observed rate increase of the reaction of epichlorohydrin with iodide ion in the presence of acetic acid was questioned by Long and Paul, who suggested that specific effects of the medium brought about by 4.0 M acetic acid may be responsible for the rate increase rather than general acid catalysis.72 However, the alternative mechanism for acid-catalyzed epoxide hydrolysis proposed by these workers, an A-l mechanism involving a carbocation intermediate, has been ruled... 

Nucleophilic ring opening of epoxides usually occurs with anti stereochemistry, with nucleophilic attack at the less substituted carbon. On the other hand, the acid-catalyzed epoxidation-hydrolysis sequence is not always stereospecific. In the case of (5 )-l-phenyloxirane (styrene oxide), the acid-catalyzed ring opening is regiose-lective and proceeds through the more stable (benzylic) carbocation there is extensive racemization because of the involvement of a carbocation. ... 

Hydroxylation by acid-catalyzed epoxide hydrolysis (Section 8.7) Anti stereochemistry occurs. 

Whereas the hydrolysis of l-chloro-2-butene gives comparable yields of products from attack of solvent at both primary and secondary carbons, very little product from the acid-catalyzed hydrolysis of butadiene oxide 10 is formed from the attack of solvent at the primary carbon. The transition state for acid-catalyzed epoxide ring opening has a relatively reactant-like geometry, and therefore positive charge de-localization into the adjacent double bond at the transition state is expected to be less than that for allyl chloride hydrolysis. 

Acetic anhydride has also been used as the acylating agent. The formation of thiiranes from thiocyanatohydrins having a tertiary hydroxy group is best achieved by p-toluenesulfonic acid-catalyzed acetylation.The analogous thiocyanatohydrins with a secondary hydroxyl and a tertiary thiocyanate function give a predominance of epoxide from thiocyanatohydrin acetates since the hydrolysis rate of the secondary acetate grouping becomes competitive with that of the tertiary thiocyanate. 

Diols can be prepared either by direct hydroxylation of an alkene with 0s04 followed by reduction with NaHSOj or by acid-catalyzed hydrolysis of an epoxide (Section 7.8). The 0s04 reaction occurs with syn stereochemistry to give a cis diol, and epoxide opening occurs with anti stereochemistry to give a trans diol. 

Epoxidation followed by acid-catalyzed hydrolysis constitutes a method for anti hydroxylation of a double bond. 

Figure 11.4 The overall result of epoxidation followed by acid-catalyzed hydrolysis is a stereospecific anti hydroxylation of the double bond. ds-2-Butene yields the enantiomeric 2,3-butanediols tra x-2-butene yields the meso compound.

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