This patent describes the 1 kg scale synthesis of a material used as a “redox shuttle” to prevent overcharging of lithium ion batteries for cars. Several PTC patents deal with reactions of phosphoryl chlorides in the presence of aqueous NaOH (including one by Halpern that uses no solvent to protect the water-sensitive compounds from water and base!) and the question always arise, how can one perform such reactions while minimizing the hydrolysis of the P-Cl bond.
In this patent, the inventors added the phosphoryl chloride over time to minimize the exposure of the water-sensitive compound to water and hydroxide. They used a significant volume of Me-THF as solvent to further dilute and minimize the contact between the P-Cl bond and water/base. They kept the reaction temperature low and that is always an important factor that PTC can use to leverage the lower energy of activation of the nucleophilic attacks, in this case by the phenoxide ion. Of course, the use of tetrabutyl ammonium cation as the phase-transfer catalyst was a key factor to enable the entire reaction.
The inventors used 2.6 equiv of the P-Cl compound instead of the 2.0 equiv theoretically required for complete reaction. It is not known if they needed that much of an excess. If they really did need that much excess, it was likely due to hydrolysis. If so, then they may have been able to reduce the hydrolysis by avoiding a phase-transfer catalyst with a bromide counterion since TBAB would form the phosphoryl bromide in-situ would be more water-sensitive and base-sensitive than the P-Cl starting material. They also may have over-agitated the reaction. The nucleophilic attack of the phenoxide on the P-Cl reactant is very likely an I-Reaction and as such only minimal agitation is required for phenoxide transfer and heat transfer to control the expected exotherm. Applying more agitation than needed results in undesired non-catalyzed interfacial hydrolysis. In addition, it is not clear why the inventors used 4 equiv of NaOH instead of 2.0 equiv that would have been enough to titrate the phenol. The excess base may also have hydrolyzed the P-Cl bond.
These considerations for PTC process improvement and others are taught in our 2-day PTC course that is taught in-house at your company which is also being taught in a public course in Cologne Germany next month.
If your company has a water-sensitive or hydroxide-sensitive reaction that requires low-cost and high-performance, you should now contact Marc Halpern of PTC Organics for PTC Process Consulting or PTC Contract Research to achieve your performance targets to the highest extent possible in the shortest development time possible.
