{beta}-Secondary and solvent deuterium kinetic isotope effects and the mechanisms of base- and acid-catalyzed hydrolysis of penicillanic acid
- Wesleyan Univ., Middletown, CT (United States)
{beta}-Secondary and solvent deuterium kinetic isotope effects have been determined at 25 {degrees}C for the alkaline and acid-catalyzed hydrolysis of penicillanic acid. In order to determine the former isotope effect, [6,6-{sup 2}H{sub 2}]dideuteriopenicillanic acid has been synthesized. In alkaline solution, the former isotope effect was found to be 0.95 {plus_minus} 0.01. These values support the B{sub AC}2 mechanism of hydrolysis with rate-determining formation of the tetrahedral intermediate that has been proposed for other {beta}-lactams. The measured {beta}-secondary kinetic isotope for the acid-catalyzed reaction was 1.00 {plus_minus} 0.01. The data indicates that a likely pathway of acid-catalyzed hydrolysis would be that of an A{sub AC}1 mechanism with an intermediate acylium ion. If this were so, the calculated {beta}-secondary isotope effect per hydrogen coplanar with the breaking C-N bond and corrected for the inductive effect of deuterium would be 1.06 {plus_minus} 0.01. This suggests an early A{sub AC}1 transition state, which would be reasonable in this case because of destabilization of the N-protonated amide with respect to the acylium ion because of ring strain. The absence of specific participation by solvent in the transition state, as would be expected of an A{sub AC}1 but not an associative mechanism, is supported by the strongly inverse solvent deuterium kinetic isotope effect of 0.25 {plus_minus} 0.00 in 1 M HCl and 0.22 {plus_minus} 0.01 in 33.3 wt % H{sub 2}SO{sub 4}. 1 fig., 3 tabs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 198127
- Journal Information:
- Journal of Organic Chemistry, Vol. 60, Issue 6; Other Information: PBD: 24 Mar 1995
- Country of Publication:
- United States
- Language:
- English
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