PTC dehydrohalogenation often needs to use a different phase-transfer catalyst to achieve optimal performance than is needed for other PTC-OH reactions such as C-alkylations. If you aware of the “Halpern pKa Guidelines for Evaluation and Optimization of New PTC Applications” (taught in the 2-day PTC course), you already know that the optimal conditions for a given PTC application depend on the structure of the substrate. That is why different PTC-OH reactions can require different phase-transfer catalyst structures. More specifically, PTC dehydrohalogenations often prefer more organophilic quats than smaller quats.
Since the biggest segment of PTC applications involves NaOH, it is very worthwhile to be knowledgeable about how to achieve the highest performance of PTC-strong base reactions. This month’s Tip will help you refine your understanding of PTC-OH systems. Understanding mechanism is often the most effective first step to optimizing performance.
The first mechanistic study of PTC-OH dehydrohalogenation (Halpern, M.; Ph.D. Thesis, Hebrew University of Jerusalem, 1983) showed that PTC dehydrobromination has an E2 mechanism. This means that an organic anion is not formed during the reaction (in contrast to most other PTC reactions) or transition state. If so, then according to the pKa Guidelines, dehydrohalogenation of a non-activated substrate should be an I-Reaction and prefer organophilic quats over smaller quats.
In fact, I used the pKa Guidelines to predict then show that tetraoctyl ammonium gives 98% dehydrobromination of substituted phenethyl bromide while TEBA (triethyl benzyl ammonium) only gives 33% conversion under the same conditions of base, catalyst loading, time and temperature (Halpern, M.; Zahalka, H.; Sasson, Y.; Rabinovitz, M.; J. Org. Chem., 1985, 50, 5088). Back in those days (1980’s), organophilic quats like tetraoctyl ammonium were rarely considered for dehydrohalogenations.
It is very important to know this in order to avoid wasting precious R&D resources and avoid performing unneeded experiments using less optimal catalysts.
Indeed, if you search the literature for PTC-NaOH reactions, you will find that many of the early publications and patents in the 70’s and 80’s used small phase-transfer catalysts, most notably TEBA (triethyl benzyl ammonium chloride). These small quats were usually ineffective for non-hydroxide applications using PTC and that is why I decided to focus my Ph.D. thesis work in the late 70’s to understanding why PTC-OH applications were different than non-NaOH PTC reactions until that time on the literature. The title of my thesis was “Hydroxide Ion Initiated Reactions Using Phase-Transfer Catalysis: Mechanism and Applications”, much of which was co-published in 15 peer reviewed publications.
In any case, even though PTC dehydrohalogenations can work with smaller quats, you might want to start screening new PTC dehydrohalogenations using more organophilic quats than smaller quats.
This is what the inventors did in the July 2014 PTC Reaction of the Month.
If you want to the best expertise available to evaluate and optimize PTC-strong base reactions to enhance your company’s profit and R&D effectiveness, now contact Dr. Marc Halpern.
