Nature of the slow step in the hydrolysis of cyclic and bicyclic ortho esters containing 1,3-dioxane rings

Abstract

A kinetic investigation is reported of the hydrolysis of a series of ortho esters containing 1,3-dioxane rings.Included are monocyclic 2-aryl-2-methoxy-l,3-dioxanes and bicyclic l-aryl-4-methyl-2,6,7-trioxabicyclo[2.2.2]octanes.Both types of compounds exhibit a change in the slow step in product formation with changing pH. At high pH the 1,3-dioxan-2-ylium ion forming step is rate determining, while at low pH the slow step involves the decomposition of the hydrogen ortho ester intermediate of the hydrolysis, and both this intermediate and the l,3-dioxan-2-ylium ion intermediate accumulate in significant amounts during hydrolysis. A similar change in the slow step has previously been observed in the hydrolysis of 2-aryl-2-alkoxy-1,3-dioxolanes. Quantitative comparison of the dioxane and dioxolanes shows that the conversion of an ortho ester (or hydrogen ortho ester) to a cyclic dialkoxycarbonium ion (three sp3 centers to sp2 centers) is more favorable for a six-atom ring than for a five-atom ring. This result is opposite that observed for reactions which convert one sp3 center to an sp2 center. The initial ring-opening stage in the hydrolysis of the bicyclo ortho esters is shown to be not reversible. This is done by generating the l,3-dioxan-2-ylium ion intermediate from a different source, a 5-(hydroxymethyl)-2-(dimethylamino)-l,3-dioxane, and finding that under the conditions of kinetic control only the dihydroxy ester product is formed. Alternate synthetic routes involving acyclic amide acetals for the preparation of the cyclic and bicyclic ortho esters are described, a major advantage of these reactions being the use of very mild acidic conditions. Also described is the use of nitrosonium tetrafluoroborate as a hydride-transfer agent with a cyclic acetal to form a 1,3-dioxan-2-ylium ion.Recent investigations in our laboratories have demonstrated that there is a change in the slow step in the overall hydrolysis of 2-alkoxy-2-aryl-l,3-dioxolanes1"3 such that under certain conditions all three reaction stages in the overall hydrolysis can be directly observed (eq 1). These ArCOOR' (!)

Hydrolysis of trioxaadamantane ortho esters. I. Dialkoxycarbocation – ortho ester equilibrium and acidity function

“…Hydrolysis in dilute acids (pH > 1) results in the appearance of a strong absorbance with A, , , at 232 nm. This new peak is due to the benzoate ester product, and the behavior here is typical of a benzoic acid ortho ester derivative (2,(21)(22)(23). What makes the trioxaadamantane very different, however, is the behavior in slightly more concentrated acids, where a new peak with A, , , at 260 nm appears (Fig.…”

“…The same absorbance is found in more concentrated acids where the cation can be characterized by nmr spectroscopy, as just discussed. Spectra with h,,, near 260 nm are also observed with other phenyl substituted dialkoxycarbocations (2,18,19,23). The other trioxaadamantanes also produce cations in moderately concentrated acids (see Experimental for A,,,).…”

Hydrolysis of trioxaadamantane ortho esters. II. Kinetic analysis and the nature of the rate-determining step

“…This first-order dependency on hydronium ion concentration is of course typical of ortho ester hydrolysis. The values of k,(app) are abnormally slow (2-phenyl-2-methoxy-1,3-dioxane, for example, has kH equal to 3.0 x lo4 M-' s-' (7) and this led to the original conclusion (2, 3) that the trioxaadamantane system is different. In terms of the mechanism, k h p p ) [7] (Table I).…”

“…[7] because of the nonideality of the reaction medium. The term in brackets represents the changing equilibrium position.…”

“…Studies conducted over the past few years (7,(10)(11)(12)(13)(14)(15)(16) have shown that the exocyclic alkoxy group OR is lost in the dialkoxy carbocationforming stage, with the key feature that ky is usually signifi- cantly smaller than both ky and k!, . The latter two are in fact quite close in magnitude, since they represent similar processes, loss of an exocyclic OR and OH to form the same cyclic cation.…”