Catalysis of Organic..

Zoeller and Barnette 389Material accountability (the sum of recovered chloropinacolone, methylpivaloyl acetate, and pinacolone) with the active Pd monophosphine and carbenecomplexes was in the range of 92-99% without accounting for impurities present inthe starting chloropinacolone. A GC-MS examination of several product mixtureswas undertaken to see if there were any additional, unanticipated by-products. Theonly additional material identified was α-methoxy pinacolone (1-methoxy-3,3-dimethyl-2-butanone). This compound was formed by methanolysis of the starting α-chloropinacolone and appears to be formed by a mixture of catalyzed anduncatalyzed processes Since this product was not anticipated, it was not quantifiedbut represents the majority of, if not the only, remaining volatile product. No attemptwas made to determine the presence of any quaternary ammonium salt formed bysimilar alkylation of the amine base by α-chloropinacolone.Improving Catalyst Performance and Reactor Productivity.The screening work demonstrated that with a (cy-hex 3 P) 2 PdCl 2 catalyst the targetedmethyl pivaloylacetate concentrations and desired reactor residence times could beachieved. Unfortunately, the process still would not meet the targeted catalystperformance (TON >5,000 mol MPA/mol Pd) and required further developmentdirected at improving catalyst and reactor productivity.Carbonylation catalysts can demonstrate complex kinetics with variant ratedetermining steps and mechanisms. However, normally carbonylation reactionsdemonstrate first order behaviors in catalyst and organic halide and zero orderdependence on alcohol. Kinetic behavior with respect to ligands and CO pressure areless predictable with inverse, zero, and first order behaviors as well as optima allbeing reported for these components. If this process follows the general trend towardfirst order behavior in the halide component and zero order in the methanolcomponent, replacing a significant volume of the methanol with α-chloropinacoloneshould lead to an increase in the catalyst turnover frequency. Replacing methanolwith reactive α-chloropinacolone would have the added benefit of increasing theconcentration of methyl pivaloylacetate in the product solution.As indicated in Table 3, reducing the excess methanol to only a 3 fold molarexcess (rendering a nearly solvent free process) far exceeded expectations andallowed significant reductions in the catalyst levels. Under these conditions, catalystturnover numbers exceeding 10,000 mol MPA/mol Pd were achieved with a turnoverfrequency of >3400 mol MPA/mol Pd/h. The reaction mixtures obtained from thisprocess formed two liquid phases and the product spontaneously separated from theamine and amine hydrochloride. As a consequence of eliminating large methanolexcesses, the methyl pivaloylacetate concentration in the product was raised to 26wt. % without additional reaction time being required. This represents an additionalca. 2.5 fold improvement in reactor productivity. No attempt was made to reduce themethanol further.