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' (!)
. 57,1531 (1979). Kinetic investigations of the hydrolysis of the 2-phenyl-4,4,5,5-tetramethyl-l,3-dioxolenium ion and 2-phenyl-2-methoxy-4,4,5,5-tetramethyl-l,3-dioxolane furnish rate constants for all three reaction stages of the ortho ester hydrolysis: ( I ) generation of the dioxolenium ion, (2) hydration of this ion to form hydrogen ortho ester, and (3) breakdown of this species t o pinacol monobenzoate. The equilibrium constant for stage (2) can also be obtained. This study complements a previous investigation of 2-phenyl-2-alkoxy-l,3-dioxolanes where similar information was obtained.The rate constants for carbonyl oxygen exchange of the ester products of these reactions, pinacol monobenzoate and ethylene glycol monobenzoate, have been measured. This reaction is shown to proceed by a different mechanism to that normally associated with exchange of carboxylic acid derivatives: cyclization of the glycol monoester to form hydrogen ortho ester, followed by loss of the labelled exocyclic OH group to give 1,3-dioxolenium ion. Reversal of these steps, initiated by an unlabelled water molecule, results in exchange. The relationship of this mechanism with that of the ortho ester hydrolysis is obvious; it is shown that the exchange provides rate constants for the reverse of stage (3). This means that both the forward and reverse rates of this process have been obtained, and this provides the equilibrium constant.
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