Hydrolysis acid-catalyzed, of epoxide

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 Sn2 attack by water. Anti stereochemistry results from the back-side attack of water on the proto-nated epoxide. 

Diols can be prepared by direct hydroxylation of an alkene with OSO4 followed by reduction with NaHSOs (Section 7.8). The reaction takes place readily and occurs with syn stereochemistry. We ll see in the next chapter that 1,2-diols can also be prepared by acid-catalyzed hydrolysis of epoxides—compounds with a three-membered, oxygen-containing ring. Epoxide opening is complementary to direct hydroxylation because it occurs with anti stereochemistry. 

CH2CH= CH2 (c) Acid-catalyzed hydrolysis of epoxides (Section 18.8)... 

A mechanism that explains some of the more important observations in the acid-catalyzed hydrolysis of epoxides 49a-d is outlined in Scheme 15. The cis/trans diol product ratios from the acid-catalyzed hydrolysis of 49a-c, which have either hydrogen- or electron-donating groups in the para position of the phenyl ring, are 74 26, 83 17 and 65 35, respectively. An intermediate carbocation 52a is trapped by azide ion in the acid-catalyzed hydrolysis of 49a and the rate constant for reaction of 52a with water in 10 90 dioxane-water solvent is estimated, by the azide clock technique, to be 1.7 x 108 s 1. Azide ion also traps an intermediate 52b in the acid-catalyzed hydrolysis of 49b, but somewhat less efficiently. The rate constant ks for reaction of 52b with solvent is estimated to be 2 x 109 s-1. The somewhat greater reactivity of 52b compared to that of 52a is consistent with the observation that... 

The acid-catalyzed hydrolysis of epoxides proceeds by either heterolytic cleavage of the carbon-oxygen bond to form a carbonium ion intermediate that subsequently reacts with water to form the diol (8, 1 mechanism) ... 

The acid-catalyzed hydrolysis of epoxides is an interesting reaction and is worth discussing in some detail. A number of lines of attack have been used in attempts to distinguish between the A-1 and A-2 mechanisms for ethylene, propylene, and isobutylene oxides. The hydrol3Tses show only specific add catalysis (Bronsted et al., 1929) and are about twice as fetst in D,0 as in HgO (Pritchard and Long, 1956b). A pre-equilibrium proton transfer... 

Acid-Catalyzed Hydrolysis of Epoxides (Section 11.9A) Hydrolysis of an epoxide derived from a cycloalkene gives a trans glycol. The reaction involves initial protonation of the epoxide O atom followed by nucleophilic attack of water and then loss of a proton to give the trans diol.The reaction also occurs with alcohol nucleophiles, and when there is a difference, reaction of the nucleophile occurs predominantly at the more substituted carbon of the protonated epoxide. 

F de Sousa (2010) Theoretical study of acid-catalyzed hydrolysis of epoxides. J Phys Chem A114(15) 5187-6194... 

Vicinal diols also occur in which the OH groups are tram. Net anti dihydroxylation occurs in a multistep process with an epoxide intermediate. The acid-catalyzed hydrolysis of epoxides yields a ring-opened product by Sj 2 attack of the nucleophihc water molecule on the protonated epoxide. We will discuss the ring-opening reactions of expoxides in the next chapter. 

Acid-catalyzed hydrolysis of an epoxide yields a trans diol (compound L) ... 

Acid-catalyzed hydrolysis of the epoxide yields a diol its stereochemistry corresponds to net anti hydroxylation of the double bond of the original alkene. 

EXAMPLE Acid-catalyzed hydrolysis of propylene oxide (epoxypropane). Step 1 Protonation of the epoxide. 

Rate coefficients of acid catalyzed hydrolysis of various epoxides in 0.69 M aqueous HC104 (tf0 = 0) at 0 °C [153]... 

Arrhenius parameters (as far as available) for the ring-opening reactions of ethylene oxide, propylene oxide, and isobutylene oxide. Overall values of ftCi and fcHcl obtained for propylene oxide have been split into rate coefficients for attack at primary carbon and attack at secondary carbon, utilizing gas chromatographic product analysis data [152]. (It is interesting to note that the results for attack at primary carbon are of the same order of magnitude as the corresponding values for ethylene oxide.) First-order rate coefficients at a constant acid concentration for the acid catalyzed hydrolysis of various epoxides [153] are collected in Table 10. Rate coefficients of the uncatalyzed and acid catalyzed reactions of ethylene oxide with various nucleophiles [151, 154] can be found in Table 11. 

The Tsi/EtO-functionalized polysiloxanes were cross-linked in the presence of trifluoromethanesulfonic acid generated in an UV-initiated decomposition of PhalOSChCFs. The process is based on acid-catalyzed hydrolysis of =SiOEt groups and formation of =SiOH functions and their subsequent condensation. We have found that the use of Ph2l0S02CF3 gave much better results than Ph2lBF4, widely used in photo-initiated polymerization of epoxides [8]. 

Problem 28.9 The following reactions have all been found to yield a mixture of pinacol and pinacolone, and in the same proportions treatment of 3-amino-2,3-dimethyl-2-butanol with nitrous acid treatment of 3-chloro-2,3-dimethyl-2-butanol with aqueous silver ion and acid-catalyzed hydrolysis of the epoxide of 2,3-dimethyl-2-butene. What does this finding indicate about the mechanism of the pinacol rearrangement ... 

Mechanisms of acid-catalyzed hydrolysis of 1-phenylcyclohexene oxides, indene oxides and 1,2,3,4-tetrahydronaphthalene-l,2-epoxides 264... 

ACID-CATALYZED HYDROLYSIS OF ALIPHATIC EPOXIDES Simple primary and secondary epoxides... 

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... 

Simple tertiary carbocations react with water/trifluoroethanol (H20/TFE) solvent with an estimated rate constant of 1012s-1, which is somewhat faster than bulk solvent reorganizes.28 Simple primary and simple secondary carbocations are predicted to be even more reactive with nucleophilic solvent than tertiary carbocations. In water solutions, therefore, the rates at which simple primary and secondary carbocations are predicted to react with solvent would exceed the rate of a bond vibration ( 1013 s-1), and consequently they would not be sufficiently stable to exist as an intermediate. An A-2 mechanism would therefore be enforced on the acid-catalyzed hydrolysis of those epoxides that potentially undergo ring opening to form primary or secondary carbocations. 

A summary of bimolecular rate constants for the acid-catalyzed hydrolysis of a series of alkyl-, vinyl- and phenyl-substituted epoxides is given in Table 1. Propylene oxide (7) is 6.6 times more reactive than ethylene oxide, and from a study of its reaction in H2018, it was shown that 70% of the glycol product results from addition of solvent to the secondary carbon and 30% from addition of solvent to the primary carbon. The reactivity per primary carbon of ethylene oxide is one-half of the observed reactivity of ethylene oxide, and thus the introduction of a methyl group on ethylene oxide results in an increase in reactivity at the primary carbon by a factor of 4 and an increase in reactivity at the secondary carbon by a factor of 9. These results are consistent with A-2 mechanisms for the acid-catalyzed hydrolyses of ethylene oxide and propylene oxide, in which some amount of positive charge generated on carbon at the transition state is stabilized by a methyl group. 

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. 

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 mechanism in Scheme 19 is somewhat speculative, and relies heavily on the assumption that axial attack of solvent is more energetically favorable than equatorial attack of solvent on carbocations similar in structure to 64. However, the stereochemistry of acid-catalyzed hydrolysis of two diastereomeric hexa-hydrophenanthrene 9,10-epoxides (65 and 67) provides support for this proposal. These two epoxides contain transfused cyclohexane moieties that restrict the geometry of each epoxide to a single conformation. Reaction of 65 with H+ yields a single carbocation conformation 66, in which the hydroxyl group is forced to occupy an axial position (Scheme 20). 

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