Catalysis of Organic..

Zoeller and Barnette 38543. Carbonylation of Chloropinacolone:A Greener Path to Commercially UsefulMethyl PivaloylacetateAbstractJoseph R. Zoeller and Theresa BarnetteEastman Chemical Company, P.O. Box 1972, Kingsport, TN 37662jzoeller@eastman.comPalladium catalyzed carbonylation of α-chloropinacolone (1) in the presence ofmethanol and tributyl amine provides a more efficient and environmentally soundprocess for the generation of methyl pivaloylacetate (2). After optimization, thepreferred catalyst, [(cyclohexyl) 3 P] 2 PdCl 2 , can be used to generate methylpivaloylacetate under mild conditions (5-10 atm, 120-130°C) with extremely highturnover frequencies (>3400 mol MPA/mol Pd/h) and very high total turnovernumbers (>10,000 mol MPA/mol Pd). The process requires very little excess amineor methanol and uses no extraneous reaction solvents. Further, extraction solventsare minimized or eliminated since the product spontaneously separates from theliquid tributylamine hydrochloride. The tributylamine can be readily recycled uponneutralization and azeotropic drying. A part of this study includes the firstdemonstrated use of a Pd-carbene complex as a carbonylation catalyst.IntroductionMethyl pivaloylacetate (2) (methyl 4,4-dimethyl-3-oxo-pentanoate, MPA) is usefulintermediate in the production of materials used in photographic and xerographicprocesses (1-6). However, current methods entail environmentally challengingmethodology. For example, current best methodology produces methylpivaloylacetate (MPA) in yields of 65-85% via a condensation of dimethyl carbonate(DMC) with a 3-5 fold excess of pinacolone in the presence of 1.5-2 fold excess of astrong base such as sodium methoxide or sodium hydride (1-3, 7-12). Unfortunately,in addition to using large excesses of reagents, these processes also utilize difficult toseparate and environmentally challenging polar aprotic solvents such as a tertiaryamides, sulfoxides, or hexaalkyl phosphoramides. The best alternative processesinvolve the addition of a dimethyl malonate or methyl aceotacetate salt, normally asthe Mg salt, to a solution of pivaloyl chloride and excess tertiary amine in ethereal orchlorinated solvents (4-6, 13-16). Unfortunately, these alternative processes (i) usemore expensive reagents while demonstrating no improvements in yield, (ii) requireexcess reagents which must be removed and recycled, (iii) generate a co-product(dimethyl carbonate or methyl acetate) and (iv) generate large Mg and amine wastestreams.