We have reported the combined use of phase-transfer catalysis with microreactors five times in the past. This is the first time we are reporting PTC with microreactors for etherification. There are several very interesting aspects to this patent application publication.
Perhaps the most notable finding is that very high selectivity is achieved when performing etherifications using reactants containing hydroxide-sensitive functional groups, such as epoxides and secondary alkyl halides, in the presence of hydroxide. The use of a microreactor with short contact time minimized hydrolysis, dehydrohalogenation and other side reactions.
Nine alkyl halides were used as alkylating agents including epichlorohydrin, 1,4-dichlorobutane, chloro-isooctane and tetrachloro-neopentane. You can imagine the need for selectivity to avoid side reactions such as hydrolysis and dehydrochlorination achieved by short contact time. Even the tetra-etherification using tetrachloro-neopentane gave 81.1% percent yield.
Another interesting aspect of this report is that several phase-transfer catalysts were screened. They include polyethylene glycol dimethyl ether, tetrabutylammonium bromide and 18-crown-6. While all the phase-transfer catalysts performed well, the reaction conditions were slightly better with the PEGDME. The molecular weight of the PEGDME was not reported.
We speculate that PEGDME was used instead of PEG in order to avoid side reactions, such as capping of the free hydroxyls of PEG by alkylation with the alkylating agents.
We have been saying for years that the combination of PTC and microreactors has great potential, especially for compounds that are sensitive to water and/or base.
Marc Halpern of PTC Organics has 47 years of experience in breakthrough PTC-NaOH applications. Now contact Marc when your company can benefit from low-cost high-performance green etherifications using phase-transfer catalysis.
