The most frustrating aspect of being a PTC expert is when I see obvious examples of reactions that should use phase-transfer catalysis that do not use phase-transfer catalysis. The reason it is so frustrating is that when process development chemists don’t use PTC for commercial applications when they should, the result is that their companies are not making as much profit or achieving the environmental performance they should be enjoying. That often results in less job security for the same process chemists who develop the process and lost green chemistry for society. Fortunately, you are a loyal reader of the PTC Tip of the Month, so this will probably never happen to you. From my experience in visiting more than 260 companies in 37 companies, I estimate that about 5%-10% of the processes that should use PTC actually do use PTC. The rest are missed opportunities for lower cost higher performance green chemistry. What a waste!
An example of a missed PTC opportunity reaction was reported this month in US Patent 9,190,493.
Even people who are not PTC experts know that one of the highest performance phase-transfer catalysis reaction categories is etherification (Williamson ether synthesis) of alcohols or phenols. Step 2a in the patent reacts hydroquinone with allyl bromide in acetonitrile using K2CO3 as base WITHOUT PTC (!!!) to produce diallyloxy benzene in 79% yield.
There are at least two compelling reasons to use PTC for this reaction. The first is that PTC always provides the opportunity to etherify phenols with alkyl halides using the lowest excess allyl halide and the shortest reaction time to achieve the highest yield with either no solvent or an easily recoverable solvent that makes two phases with water to achieve easy less expensive work up. Those multiple simultaneous benefits are enough to always consider PTC for etherification of phenols in all cases.
The second reason has to do with selectivity and may be less obvious. PTC excels in dietherification of diphenols like hydroquinone. Let’s understand why.
When PTC is used to etherify hydroquinone with allyl bromide (by the way, allyl chloride would be less expensive, though one must be set up to handle the safety issues) in the presence of potassium carbonate, the phase-transfer catalyst transfers the hydroquinone anion from the surface of the potassium carbonate to the bulk organic phase where it forms the allyl ether. Once the monoallyl ether is formed, the phase-transfer catalyst “has a choice” between transfering a non-allylated hydroquinone dianion or the monoanion of hydroquinone monoallyl ether. The phase-transfer catalyst will always choose the more organophilic anion which in this case is the monoanion of hydroquinone monoallylether since it has more carbons and only one negative charge whereas the hydroquinone dianion is more polar and less organophilic.
As a result, when etherifiying hydroquinone under PTC conditions, only a very small steady state concentration of hydroquinone monoallyl ether is present and the diallyl ether is very selectively formed. In fact, the etherification of hydroquinone with allyl halide using phase-transfer catalysis should proceed to 100% completion under mild conditions with very high atomic efficiency (low excess of allyl halide) and provide the opportunity to choose any convenient organic solvent, including solvent free.
It is possible that the chemists who reported this etherification in US Patent 9,190,493 did not need the absolute best reaction conditions. But even so, whenever chemists do not leverage the most well-known advantages of phase-transfer catalysis for obvious applications, you have to wonder what else they are missing for the benefit of their employers that could save their jobs.
To assure that your company does not miss PTC opportunities to increase profit, process performance and R&D efficiency, now contact Marc Halpern of PTC Organics to inquire about integrating highly specialized expertise in industrial PTC with your process development programs.
