Sometimes, the role of the quat bromide phase-transfer catalyst is to deliver the bromide which is the real catalyst for the reaction.
In prior art, the condensation reaction shown was performed at 170 C with no solvent and formed two impurities, one of which was formed at an unacceptable level of more than 20%. The inventors wanted a more selective reaction and achieved that by reducing the temperature by 60 C to 110 C and by diluting the reactants in a solvent.
The solvent used was toluene and the catalyst was bromide, presumably to form the more reactive benzoyl bromide in situ. Since NaBr or KBr are not soluble in toluene, tetrabutylammonium bromide was used.
It is interesting to note that the phase-transfer catalysts are claimed explicitly in the patent claims as “tetra alkyl ammonium halide is selected from a group comprising tetra butyl ammonium bromide, tetra ethyl ammonium bromide, tetra butyl ammonium chloride and tetra butyl ammonium iodide or any combination thereof; and wherein the benzyl tri alkyl ammonium halide is benzyl tri alkyl ammonium bromide.” If indeed bromide is the catalyst, then iodide would be better and chloride would not be useful. Iodide is claimed, but so is chloride. We speculate that chloride was included in the claims to be comprehensive or misleading.
It is further interesting that benzyl trialkyl ammonium halide was specified to be bromide while chloride was not explicitly mentioned. The reason that this is particularly interesting is that benzyl trialkyl ammonium salts are MUCH less expensive in the chloride form due to the reaction of the trialkylamine with benzyl chloride that is preferable over benzyl bromide for both cost and safety reasons.
Thus, we speculate that the explicit citation of bromide for benzyl trialkyl ammonium halide may be a hint that bromide in the real catalyst and that the less expensive and more ubiquitous chloride is simply not effective.
In this condensation, the main byproduct being minimized is the bis-salicylamide shown below, suggesting that the mechanism proceeds through N-acylation first followed by ring closure.
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