This patent describes the synthesis of the compound mesitrione. The fifth step of six chemical steps is the PTC acylation of the sodium salt of cyclohexanedione. The cyclohexanedione anion reacts at the enol oxygen with a water-sensitive benzoyl chloride.
Acyl chlorides are sensitive to hydrolysis and the inventors note that they worked at low temperature between 0 C and 15 C to avoid hydrolysis. They describe three different sets of conditions that give 92%-94% yield.
The inventors do not highlight the advantage of PTC in this system which is the use of the phase boundary to protect the acyl chloride from water by dissolving the organic acyl chloride in dichloroethane that is immiscible with water. The phase-transfer quat cation transfers the cyclohexanedione anion into the bulk organic phase where it reacts with enhanced reactivity with the acyl chloride with little to no hydration and little to no hydrolysis.
We speculate that the inventors chose to add solid sodium salt of cyclohexanedione in the first set of conditions (“Conditions A”) in order to minimize the amount of water in the system and thus minimize hydrolysis. The inventors were even bolder in Conditions B and C by adding the sodium salt of cyclohexanedione as a 28% aqueous solution, first at 2 C, then at 5 C.
The inventors did not describe their agitation system, but we would recommend avoiding over-agitation since that would cause non-catalyzed interfacial hydrolysis.
Further optimization of this PTC acylation should be possible, focused on reducing the excess sodium salt of cyclohexanedione while achieving a yield in the high 90’s. If your company needs to achieve high yield of reactions using water-sensitive compounds in the presence of water, now contact Marc Halpern of PTC Organics to benefit from highly specialized expertise in developing low-cost high-performance green chemistry processes using phase-transfer catalysis, specifically for water-sensitive compounds.
