Catalysis of Organic..

392 Carbonylation of ChloropinacoloneaConditions: 33.0 mL chloropinacolone, 90 mL Bu 3 N, 31.0 mL MeOH; catalyst:14.0 mg (0.019 mmol) (cy-hex 3 P) 2 PdCl 2 + 28.0 mg. (0.1 mmol) of cy-hex 3 P, 3 h, COpressure, and temperature as indicated.bP co (partial CO pressure) calculated by subtracting the partial pressure of MeOHand Bu 3 N from the total pressure.The selectivity loss observed with either elevated temperature or elevatedpressure was likely due to competing formation of α-methoxy pinacolone viamethanolysis. Whereas the GC peak assigned to α-methoxy pinacolone was only atrace component in reactions operated at low pressure and at 120-130°C, the peakassigned to α-methoxy pinacolone became quite significant at conditions entailinghigh temperature, high pressure, or both.The earlier work on chloroacetone (18,19) already indicated that trialkylamines were superior to other bases for this reaction. Therefore the decision to usetrialkyl amines to scavenge HCl was already determined by the literature precedent.However, when compared to the tributyl amine, smaller amines might be preferredsince they could boost the reactor productivity by reducing the volume.Unfortunately, for unknown reasons, the process did not work as well with thesimpler amines. Both tripropyl amine and triethyl amine displayed both lower ratesand lower selectivity for methyl pivaloyl acetate. (See Table 6.)Table 6. Effect of Using Simpler Amines aSelectivityEntry BasePressure(atm) Conversion MPA PA TON1 Et 3 N 9.5 b 88% 68% 2.3% 80202 Bu 3 N 8.5 b 89% 88% 3.7% 102803 Pr 3 N 5.4 65% 83% 2.4% 71104 Bu 3 N 5.4 78% 91% 3.2% 9450aConditions: 33.0 mL chloropinacolone; 378 mmol of amine; 31.0 mL MeOH;catalyst: 14.0 mg (0.019 mmol) (cy-hex 3 P) 2 PdCl 2 + 28.0 mg. (0.1 mmol) of cyhex3 P; 120°C, 3 h, CO gauge pressure as indicated.bP co (calc.) = 4.4 atm. (accounting for solvent vapor pressure.)In a commercial process, product recovery in this newly developed processwould be simple since most of the product spontaneously separates into two liquidlayers and only a minor amount of product is retained in the amine hydrochloridephase upon acidification of the remaining excess amine. Therefore, no additionalsolvent is required although a small amount might be used to extract the minorportion of product retained in the amine hydrochloride layer. (Any minor amount ofproduct remaining in the tributylamine hydrochloride layer may be recycled with theamine and recovered in the subsequent batches.) Final product purification is readilyachieved by distillation and any unreacted α-chloropinacolone can be recycled tosubsequent batches. Neutralization of the Bu 3 N . HCl layer with NaOH regeneratestributyl amine with varying amounts of the Pd still being retained in the amine. The