Example 14 of this 20-year old patent describes the high yield chlorination shown in the diagram on an 800 lb scale. PTC is used to deprotonate fluorene (pKa 23) with NaOH and the quat-fluorenyl anion ion pair attacks carbon tetrachloride to form 9-chlorofluorene. The 9-chlorofluorene is more acidic than fluorene and undergoes rapid chlorination by the same mechanism. One molecule of carbon tetrachloride provides one chlorine atom. The atomic efficiency is very high.
The phase-transfer catalyst used was tetrabutylammonium hydroxide. The inventor did a nice job in showing that tetrabutylammonium bromide (TBAB) is NOT an effective phase-transfer catalyst for this reaction. Since this is not an academic paper, she does not speculate why but we speculate that the reason is that bromide hinders the extraction of hydroxide. As we teach in our 2-day PTC course, the affinity of the tetrabutylammonium cation for bromide is about 3,000 times more than for hydroxide.
We do not like to use the hydroxide form of tetraalkylammonium salts due to both high cost as well as the potential for decomposition by Hofmann Elimination during storage. The inventor concluded that quat hydroxides are better than quat bromides and that is a good conclusion, but there may be better alternatives.
We expect this reaction to be a T-Reaction based on the “Halpern pKa Guidelines for Evaluation and Optimization of PTC Applications.” Accordingly, we expect “accessible” quat cations with a q-value of about 1.75 to work better than tetrabutylammonium. If we had to do this reaction today, we would screen the use of methyl tributyl ammonium chloride (MTBAC) as the phase-transfer catalyst. It is possible that the chloride will also hinder hydroxide extraction, though to a much lower degree than bromide. We would be very curious about the combination of MTBAC with 50% NaOH for this reaction. MTBAC also washes into water more easily during workup which minimizes aqueous waste.
Now contact Marc Halpern of PTC Organics if your company wants to achieve higher profit and improved process performance for strong base reactions that you expect may be improved using phase-transfer catalysis.
