Influence of Alkoxy Groups on Rates of Acetal Hydrolysis and Tosylate Solvolysis

Electrostatic Stabilization of Developing Oxocarbenium Ion Intermediates and Neighboring-Group Participation to Form Oxonium Ions

Angie Garcia, Douglas A L Otte, Walter A. Salamant, Jillian R. Sanzone, Keith Woerpel

Research output: Contribution to journalArticle

Abstract

The hydrolysis of 4-alkoxy-substituted acetals was accelerated by about 20-fold compared to that of sterically comparable substrates that do not have an alkoxy group. Rate accelerations are largest when the two functional groups are linked by a flexible cyclic tether. When controlled for the inductive destabilization, an alkoxy group can accelerate acetal hydrolysis by up to 200-fold. The difference in rates of acetal hydrolysis between a substrate where the alkoxy group was tethered to the acetal group by a five-membered ring compared to one where it was tethered by an eight-membered ring was less than 100-fold, suggesting that fused-ring intermediates were not formed. By comparison, the difference in rates of solvolysis of structurally related tosylates were nearly 10<sup>6</sup>-fold between the five- and eight-membered ring series. This observation implicates neighboring-group participation in the solvolysis of tosylates but not in the hydrolysis of acetals. The acceleration of acetal hydrolysis by an alkoxy group is better explained by electrostatic stabilization of intermediates that accumulate positive charge at the acetal carbon atom. (Chemical Presented).

Original languageEnglish (US)
Pages (from-to)4470-4480
Number of pages11
JournalJournal of Organic Chemistry
Volume80
Issue number9
DOIs
StatePublished - May 1 2015

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Acetals
Static Electricity
Electrostatics
Hydrolysis
Stabilization
Ions
Substrates
alkoxyl radical
hydronium ion
Functional groups
Carbon
Atoms

ASJC Scopus subject areas

  • Organic Chemistry
  • Medicine(all)

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Influence of Alkoxy Groups on Rates of Acetal Hydrolysis and Tosylate Solvolysis : Electrostatic Stabilization of Developing Oxocarbenium Ion Intermediates and Neighboring-Group Participation to Form Oxonium Ions. / Garcia, Angie; Otte, Douglas A L; Salamant, Walter A.; Sanzone, Jillian R.; Woerpel, Keith.

In: Journal of Organic Chemistry, Vol. 80, No. 9, 01.05.2015, p. 4470-4480.

Research output: Contribution to journalArticle

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