tert-Butyl phenyl ketone (CAS NO.: ), which is known as 1-Propanone, 2,2-dimethyl-1-phenyl, could be produced through the following synthetic routes.

A. phenylthio(tert-butyl)cuprate. A dry, 200-ml., round-bottomed flask is fitted with a magnetic stirring bar and a 100-ml., pressure-equalizing dropping funnel, the top of which is connected to a nitrogen inlet. After the apparatus has been flushed with nitrogen, 50 ml. of 1.60 M (0.080 mole) n-butyllithium solution is placed in the flask and cooled with an ice bath. Under a nitrogen atmosphere, a solution of 8.81 g. (0.0801 mole) of freshly distilled thiophenol in 30 ml. of anhydrous tetrahydrofuran is added dropwise to the cooled, stirred solution. An aliquot of the resulting solution is standardized by quenching in water, followed by titration with 0.10 N hydrochloric acid to a green end point with a bromocresol indicator. The concentration of lithium thiophenoxide prepared in this manner is typically 1.0 M.

A dry, 250-ml., three-necked round-bottomed flask is equipped with a sealed mechanical stirrer, a glass stopper, and a rubber septum through which are inserted hypodermic needles used to evacuate the flask and to admit nitrogen. After the apparatus has been flushed with nitrogen, 4.19 g. (0.0220 mole) of purified copper(I) iodide is added, and while warming with a flame, the apparatus is evacuated, then refilled with nitrogen. After this procedure has been performed twice, the flask is allowed to cool, the stopper is replaced with a thermometer, and 45 ml. of anhydrous tetrahydrofuran is added with a hypodermic syringe. With continuous stirring, 22 ml. of 1.0 M (0.022 mole) lithium thiophenoxide solution is added with a syringe to the slurry of copper(I) iodide. After 5 minutes, the resulting yellow solution is cooled, with continuous stirring, to -65° with an acetone–dry ice cooling bath. Some copper(I) thiophenoxide usually separates from solution at ca. -45°. When the temperature of the mixture has reached ca. -65°, 13.6 ml. (0.0218 mole) of 1.60 M tert-butyllithium solution is added with a syringe to the stirred mixture at such a rate that the temperature of the mixture remains at -60° to -65°. The resulting cloudy yellow-orange solution of the cuprate reagent is stirred at -60° to -65° for 5 minutes.

B. tert-Butyl phenyl ketone (CAS NO.: ). With a syringe a solution of 2.81 g. (0.0200 mole) of freshly distilled benzoyl chloride in 15 ml. of anhydrous tetrahydrofuran is added dropwise, with stirring, to the cold solution (-60° to -65°) of the cuprate reagent. The resulting yellow-brown solution is stirred for 20 minutes (at -60° to -65°) and quenched by the addition, with a syringe, of 5 ml. of anhydrous methanol. The red-orange reaction mixture is allowed to warm to room temperature and then poured into 100 ml. of aqueous saturated ammonium chloride. The copious precipitate of copper(I) thiophenoxide is separated by suction filtration and washed thoroughly with several 50-ml. portions of diethyl ether. The combined filtrate is extracted with three 100-ml. portions of ether. The combined ethereal solution is washed with two 50-ml. portions of aqueous 1 N sodium hydroxide and with one 50-ml. portion of aqueous 2% sodium thiosulfate. Each of the aqueous washes is extracted in turn with a fresh 50-ml. portion of ether. The combined ethereal solution is dried with anhydrous magnesium sulfate, filtered, and concentrated by distillation through a short Vigreux column. The residual pale yellow liquid is distilled through a short column under reduced pressure, yielding 2.73–2.82 g. (84–87%) of tert-butyl phenyl ketone as a colorless liquid b.p. 105–106° (15 mm.), 114–115° (44 mm.), n²⁰D 1.5092, n²⁵D 1.5066.

Notice: tert-Butylithium is extremely pyrophoric and must not be allowed to come into contact with the atmosphere. This reagent should only be handled by individuals trained in its proper and safe use. It is recommended that transfers be carried out by using a 20-mL or smaller glass syringe filled to no more than 2/3 capacity, or by cannula. For a discussion of procedures for handling air-sensitive reagents, see Aldrich Technical Bulletin AL-134.

Caution! Since the odor of the thiophenol (benzenethiol) used in this preparation is unpleasant, both steps of this preparation should be conducted in a hood and the glassware used should be washed before it is removed from the hood.