Last week, someone asked about tetrabutyl ammonium chloride (“TBAC”) on a process chemistry group on LinkedIn. In our experience, if someone is using TBAC, there is at least a 90% probability that there is an opportunity to improve the process. There are several reasons for this.
First, we should point out that TBAC is more expensive than TBAB (tetrabutyl ammonium bromide). Why? When you try to react tributylamine with butyl chloride directly, you get nearly exclusively dehydrohalogenation and irreversibly create butene, so you do not make TBAC. In contrast, if you react tributylamine with butyl bromide in one of a few selected solvents under the right conditions, you can make TBAB in very high yield with very little loss to dehydrohalogenation.
If you want to convert TBAB into TBAC, you must climb a thermodynamic hill since the tetrabutyl ammonium cation prefers to pair with bromide about 10 times more than with chloride. So, you would need to do multiple expensive ion exchange extractions or use a countercurrent extraction. In any case, it is expensive.
On top of that, TBAC is hygroscopic and hard to keep dry or in its low hydrated form.
As a result, TBAC is often made from TBA hydrogen sulfate, since it is easier to exchange hydrogen sulfate for chloride. But that is expensive too.
Those are just reasons for why TBAC is expensive. But there are usually more compelling reasons for using other phase-transfer catalysts other than TBAC. They have to do with the nature of PTC applications, especially nucleophilic substitutions and most PTC strong base reactions that generate a leaving group.
Those reasons will be described in next month’s PTC Tip of the Month. Feel free to send an E-mail directly to Marc Halpern if you think you know why it is almost never optimal to use expensive TBAC as a phase-transfer catalyst for most PTC nucleophilic substitution applications. If you provide a “right answer”, let us know if we can publish your name as having given a right answer.
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.
