Thiazolidine Ring-Opening: Baldwin's Rules and Rate-determining Proton Transfer

Rory A. More O Ferrall 1Eileen McManus Annemarie Lawley Deirde O. Brien Youssef Khalifa Sasha Gorolev Shinjiro Kobayashi 

1. University College Dublin, Dublin, Ireland


The 4-dimethylaminophenyl substituted thiazolidine 1 is subject to pH-dependent ring-opening and ring-closing equilibria yielding the resonance stabilised thiol iminium ion 2 and diprotonated thiazolidine 3 shown in Scheme 1.

2.jpg Scheme 1

Rate constants for ring-opening or ring-closing can be measured spectrophotometrically using stopped flow or temperature jump fast reaction techniques taking advantage of the absorption of the iminium ion at λmax= 400nm. In the ring-opening direction the reaction is acid-catalysed at low pH but becomes inversely dependent upon acid concentration above pH 1.5 and independent of acid concentration above pH 3.5.

The inverse acid dependence is consistent with a rapid deprotonation of the thiol group of the iminium ion 2 followed by rate-determining ring-closure, as shown in Scheme 2. The pH-independent reaction implies that at low acid concentrations the deprotonation step becomes rate-determining. This is a rare example of rate-determining proton transfer between electronegative atoms (S and H2O) and is confirmed by pronounced catalysis by buffer acids in carboxylic, cacodylic, imidazole and lutidine buffers.


Scheme 2

Assignment of a rate constant k-1 = 3 x 1010 M-1s-1 for protonation of the thiolate anion by H3O+ implies a rate constant k2 = 107 s-1 for closing of the thiazoldine ring. This is a large rate constant for a 5-endo trig transformation, which is formally disfavoured by Baldwin's rules. Interestingly, the rate constant is reduced by factors of up to 108-fold by replacing the N-H of the thiazoldine ring by N-butyl or N-phenyl groups. The interpretation of these results will be discussed.

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Presentation: oral at 18th Conference on Physical Organic Chemistry, Symposium 2, by Rory A. More O Ferrall
See On-line Journal of 18th Conference on Physical Organic Chemistry

Submitted: 2006-05-26 09:28
Revised:   2009-06-07 00:44
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