One of the inventions reported in this patent is the efficient etherification of 9,9-bis(hydroxymethyl)fluorene with dimethyl sulfate using 50% NaOH and phase-transfer catalysis. The inventor did a good job in minimizing hydrolysis of the DMS but could have done better with just one additional simple choice.
Dimethyl sulfate is an effective methylating agent but can obviously decompose when attacked by NaOH. Phase-transfer catalysis provides the opportunity to protect dimethyl sulfate from hydrolysis by dissolving it in toluene, that rejects water and hydroxide, then using the phase-transfer catalyst to transfer the alkoxide of 9,9-bis(hydroxymethyl)fluorene from a solid phase, omega phase or concentrated aqueous phase into the toluene phase.
Nevertheless, some interfacial hydrolysis can still occur between the dimethyl sulfate located in toluene and the NaOH in the aqueous or solid phase.
Adding dimethyl sulfate in 4 portions resulted in yield increase from 44% to 80%. When adding the DMS is 1-2 portions, too much DMS was hydrolyzed. When the DMS is hydrolyzed, it consumes NaOH, so more is needed to complete the reaction.
In addition, the inventor found that a time interval was needed for etherification in between portion additions, otherwise adding more DMS just resulted in more hydrolysis.
The inventor reported that the preferable number of equivalents of dimethyl sulfate is 3.5-4.5. Since 2 equiv are needed in theory, some DMS decomposition is likely occurring. They also used 5.65 equiv of NaOH (too much for preventing hydrolysis?).
This is a solid-liquid PTC reaction and a thick paste was formed that presumably consists of excess NaOH, alkoxide salt and dialkoxide salt of the bishydroxymethyl fluorene.
The bromide of TBAB may also contribute to the decomposition of the dimethyl sulfate, forming the less reactive and volatile methyl bromide. Therefore, we would recommend screening tetrabutylammonium hydrogen sulfate for this reaction since one objective of the patent is to minimize the excess dimethyl sulfate. I learned this the hard way when I performed more than 100 PTC alkylations with dimethyl sulfate in the 1970’s.
No mention was made of the nature of agitation in this system. Typically, PTC reactions that involve water-sensitive compounds or hydroxide-sensitive compounds are better performed with just enough agitation to achieve adequate heat transfer to be safe, otherwise non-catalyzed interfacial hydrolysis can reduce profitability and increase waste.
Now contact Marc Halpern of PTC Organics to help your company achieve low-cost high-performance green chemistry using phase-transfer catalysis and extract the most profit from your strong base reactions, nucleophilic substitutions, oxidations and reductions.
