Outstanding mechanistic work was done by phase-transfer catalysis pioneers in the 1970’s and some of this early work has great value that is directly applicable to developing commercial PTC processes today. One such surprising and fascinating behavior that LOOKS LIKE IT’S AUTO-CATALYTIC was reported in Starks’ classic landmark paper: Starks, C.; Owens, R.; J. Amer. Chem. Soc., 1973, 95, 3613.
The reaction studied was the simple nucleophilic substitution between sodium cyanide and 1-bromooctane to form 1-cyanooctane. When using tetrabutyl phosphonium bromide (TBP Br) as the catalyst, the reaction starts very slowly and speeds up as conversion increases, just like an autocatalytic reaction. Conversions were 10% at 1 hour, 20% at 2 hours, 67% at 3 hours and 97% at 3.5 hours. That is a remarkable increase in reaction rate and is opposite to normal reactions that slow down as conversion increases.
Even though this looks like autocatalytic behavior, there is a simple explanation that is worthwhile to know since it applies to many solvent-free PTC reactions. Following is the valuable lesson that is applicable to solvent-free PTC reactions. In fact, some of you may have encountered this behavior in the lab, pilot plant or plant and maybe wondered why and how to design the reactor.
TBP Br is “relatively insoluble in 1-bromooctane but highly soluble in 1-cyanooctane.” In a true PTC system, the reaction takes place in the organic phase and the role of the phase-transfer catalyst is to transfer the reacting anion into the bulk organic phase. If the TBP cation is not in the organic phase, it can’t catalyze the reaction very well except at the interface. As the reaction proceeds, the organic phase contains more and more cyanooctane and the TBP cation becomes more and more soluble in the organic phase (= reaction phase), carrying with it the cyanide raectant. Hence, the reaction gets faster and faster at higher conversions DUE TO INCREASING SOLUBILITY IN THE ORGANIC REACTION PHASE AS THE SOLVENT CHANGES IN THE SOLVENT-FREE PTC SYSTEM. This behavior was confirmed using C-14 labeled TBP Br.
To make this more interesting, when Starks used tributyl hexadecyl phosphonium bromide (TBHDP Br), typical perfect pseudo-1st order kinetics were observed throughout the reaction including nearly 80% conversion at 1 hour (> 50% conversion at 20 min). This is totally consistent with the extraction mechanism and in fact, Starks proved the extraction mechanism (as much as a mechanism can be proved) in this publication with in-depth kinetic studies examining multiple aspects of the reaction. Starks coined the term “phase-transfer catalysis” and proposed the extraction mechanism.
Clearly, this paper and Starks’ earlier paper from 1971 are the most important foundation publications in the history of phase-transfer catalysis. If you haven’t read this publication lately, get a copy and read it. It’s an extremely compelling “scientific work of art.”
If your company can benefit from achieving higher process performance in a shorter development time by having access to the best PTC expertise available, now contact Marc Halpern by E-mail to inquire about using phase-transfer catalysis to achieve low-cost high-performance green chemistry.
If you’re not sure if PTC can help your reaction, now fill out the form shown at http://phasetransfer.com/projectform.pdf and send it to Marc Halpern by fax at +1 856-222-1124 or by E-mail of a scanned copy. If we do not have a secrecy agreement already in place, please use “R-groups” instead of the exact chemical structures.
