How to diagnose non-elementary kinetics in acid-catalyzed ester hydrolysis data

[Nora.M]

I'm an undergraduate chemistry student working on a project studying the acid-catalyzed hydrolysis of an ester, and my experimental rate data isn't fitting neatly to simple first or second-order models. I suspect there might be a more complex mechanism at play, perhaps involving an intermediate or a change in the rate-determining step. For those with experience in kinetic analysis, what are the best practical approaches for diagnosing a non-elementary reaction from experimental data, and how did you proceed to propose and test a plausible multi-step mechanism?

[Harper.W]

Nice project. Here's a practical diagnostic workflow you can try: first gather time-course data at several [ester] and several [H+], then compute initial rates and plot log(rate) vs log([ester]) and log([H+]) to estimate reaction order. If the orders aren’t clean integers or vary with conditions, that flags a non-elementary mechanism. Next, map a pH-rate profile over a wide range to see if the rate dependence changes, which often hints at pre-equilibria or multiple steps. Do a solvent isotope experiment by running a parallel set in D2O; a noticeable kinetic isotope effect suggests proton transfer is involved in the rate-determining step. Test a few different esters to probe substituent effects. Finally, pick two plausible multi-step mechanisms, derive their rate laws, and fit your time-course data globally. Compare fits with AIC/BIC and pick the simplest model that explains all datasets.