P-Cresol → 4-Methyl-2-t-octylphenol

Participants

Reaction Conditions

Reaction Steps

Preparation was modified from the method of Kitchen, L. J., J. Am. Chem. Soc. 1948, 70, 1290. In a round-bottom flask to which were attached two addition funnels, a mixture of p-cresol (33.12 g, 306 mmol) and 33 mL 2,4,4-trimethyl-1-pentene was purged with nitrogen. The flask was cooled to 0° C., and 162 mL additional olefin (total amount of 2,4,4-trimethyl-1-pentene=1.23 mol, 4.0 eq.) was added dropwise, while a mixture of boron trifluoride etherate (5 mL, 40 mmol) and 30 mL nitrogen-sparged hexanes was added at the same time. The addition of olefin proceeded for 160 min, and subsequently the flask was allowed to warm to room temperature, and then was heated to 45° C. with stirring under nitrogen for 16 h. After cooling back to room temperature, the reaction was quenched by the addition of 121 g of 30% NaOH/H2O and 10 mL hexanes. After separation, the organic fraction was washed with water, and the combined aqueous fractions were washed with hexanes. The combined organic fractions were again washed with water and then distilled. The fraction distilling at 141° C. and 9-10 Torr was saved and analyzed. Yield: 30.56 g waxy white solid (45%). M.P.=42-5° C. 1H NMR was in accordance with literature (PCT Int. Appl. WO 2006120178 A1, inventors Olesen, Preben. H.; Hansen, H. C.; Christiansen, L. B.; Nielsen, F. E.; Petersen, A. K., to Novo Nordisk A/S).

Provenance & Evidence