Rate determining orthoesters

It seems probable that this picture is relevant to ester hydrolysis, and the above conclusions make good sense chemically. But it must be realised that the comparison of trialkyl and monoalkyl orthoesters involves a not-inconsider-able extrapolation. The latter are presumably intermediates in the hydrolysis of trialkyl orthoesters, and their hydrolysis is clearly considerably faster than that of the fully esterified compounds, since the loss of the first alkyl group is rate-determining. In particular, concerted elimination mechanisms, illustrated in (24)... 

The acid-catalyzed hydrolysis of orthoesters is very much faster than that of esters. The second-order rate coefficient for the hydrolysis of ethyl acetate is of the order of 10"4 1-mole-1-sec1 at 25°C, whereas that for the hydrolysis of ethyl orthoacetate103 is of the order of 104 l-mole-1-sec 1, and that for the breakdown of a monoalkyl orthoester must be faster still. If the breakdown of the tetrahedral intermediate is partially rate-determining in acid-catalyzed ester hydrolysis, therefore, its concentration must be very small that is, the equilibrium for its formation must be highly unfavourable. This... 

The most probable mechanism for the rate determining step involves a transition state, such as 3, in which the proton transfer either precedes or is concerted with covalent bond breaking. The mechanisms of orthoester hydrolysis have been summarized and discussed by DeWolfe and Jensen (1963), Wenthe and Cordes (1964), Bunton and DeWolfe (1966), Cordes (1967), DeWolfe (1969), and Jencks (1969). 

The hydrolysis reactions of acetals, ketals, and orthoesters are catalyzed by acids but not by bases. It has been found that these three groups of substrates are hydrolyzed via a common general mechanism — involving similar types of intermediates — though the rate-determining step may vary from case to case. In the hydrolyses of ethyl orthoacetate, orthopropionate, and orthocarbonate, general acid catalysis was unambiguously established for the first time by Bronsted and Wynne-Jones [158]. 

In the NMR experiments carried out by Wenthe and Cordes [187] with methyl orthobenzoate and methyl orthocarbonate in CD3OD—D20 solutions, the rate coefficients for the disappearance of orthoester and those for the formation of CH3OD and of carboxylic ester have been found identical within experimental error (Table 15). This indicates that there is no exchange of methoxy groups prior to hydrolysis. The same result has been obtained from product analysis studies of the carboxylic esters formed. Consequently, the rate-determining step must be carbonium ion formation or a previous step. The findings do not support an A2 mechanism, for the following reason. As the nucleophilic reactivities of water and methanol are similar, the A2 reaction with attack of water... 

This mechanism via an oxacarbenlum Ion Is an Si)l mechanism. If the monomolecular cleavage of the blcycllc oxonlum Ion Is the rate-determining step. A variant of this mechanism will be discussed later In the case of the polymerization of blcycllc orthoesters. 

Second-order rate coefficients, kH (= rate/[S] [H30+]), for the hydrolyses of some typical acetals, ketals, and orthoesters in purely aqueous solutions are collected in Table 12. In a compilation of data from one single source [162], ftH values can be found for the reactions of a large number of diethyl acetals and ketals in 50 % dioxane—water at 25 °C. In more recent studies, kH values have been determined for the hydrolyses of substituted benzaldehyde diethylacetals [163] and benzophenone diethyl-ketal [164] in the same solvent (Table 13). The hydrolyses of para-substituted methyl orthobenzoates have been studied in 70 % methanol-water [169]. A large amount of other work is concerned with various special examples. 

The A2 mechanism can be excluded with certainty for the hydrolyses of all orthoesters discussed. This is done on the basis of the determined volume of activation, AF = +2.4 cm3 (Table 1) for ethyl orthoformate [32], on the basis of the strongly increased rate in comparison to orthoformate (no steric hindrance) for orthoacetate and orthopropionate, and on the basis of the results of experiments with added nucleophiles for orthobenzoate [183] and orthocarbonate [192]. The observed AS values (Table 12) are in agreement with these conclusions. Consequently, the mechanism of orthoester hydrolysis must be either A1 or A-SE2, or possibly a concerted process with proton transfer and carbonium ion formation in the same step. 

Additions of acetals and orthoesters to enol ethers probably represent the most intensively studied class of Lewis acid promoted reactions in the chemistry of aliphatic compounds. Since usually catalytic amounts of BFg OEta have been employed, concentration control (rule A) should predominate. Unlike the solvolyses of alkyl halides, the acid catalyzed hydrolyses of acetals and orthoesters do not follow a rate equilibrium relationship so that the corresponding hydrolysis rates cannot be used for the analysis of electrophilic addition reactions. We have, therefore, carried out competition experiments to determine relative reactivities of acetals and orthoesters towards methyl vinyl ether in presence of catalytic amounts of BF3 0Et2 (Figure 11). As the reactivity order towards other ir nucleophiles can be expected to be similar, the krei values of Figure 11 can be used to rationalize or predict the results of acetal and orthoester additions 1 1 Adducts can only be generated selectively if the k ei values of the designed products are smaller than the k Qi values of the reactants. 

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